Category Archives: Genetic Therapy

Autoplay

Show Thumbnails

Show Captions

Ahwatukee Foothills parents Kendra and Dave Riley have spent most of their recent days staying at their hotel, taking their baby daughter to the nearby hospital, and making weekly trips to Amsterdam for their other daughter's medical treatment.

It's a routine they weren't expecting three months ago.

So much has changed for them since the early months of the pandemic, when the couple's middle daughter, Olivia, was diagnosed with a rare genetic disorder called metachromatic leukodystrophyf, or MLD.

Later, as Olivia began losing the ability to move and communicate, the Rileys learned their youngest daughter, Keira, also has the same disease. The Rileys flew to Milan weeks ago for an opportunity they almost missed: Gene therapy treatment that could save Keira's life.

Kendra said work flexibility helped her rearrange her family's life. She runs her own public relations company, Dawning PR, after years promoting businesses in the food and beverage industry.Prior to starting her own business, she did in-house PR for Lon's at the Hermosa Inn and helped promote Clever Koi when it first arrived onto the Phoenix dining scene.

Now, thanks to the generous donations of her community and a bit of luck as they raced against time to secure their visas in a pandemic the Rileys have a chance to start treating Keira early while moving Oliva's treatment overseas.

"I mean, every day is truly unreal to us," Kendra said in a phone call from Milan. "Yes, were handling it and moving forward and being strong for our girls. But there's not a day that goes by where I dont think, is this really happening?"

Kendra said it's been difficult to predict how each day will be because it depends on Olivia. Her middle daughter might be happy one minute, then crying the next because she's in pain or frustrated that she can't move the way she used to, Kendra said.

The support of Kendra's parents and volunteers have helped the Rileys with their day-to-day needs in Europe.

"It's mentally draining," Kendra said. "Your heart hurts when you see your child in pain."

"We didnt know what 'It takes a village' meant until we had a daughter with special needs. It truly does take a village to keep our household going," she added.

Kendra first noticed something seemed out of ordinary when Olivia appeared to have trouble walking. Olivia was about 18 months old and taking steps seemed to cause her pain. About the end of February, Kendra noticed that Olivia's irises seemed to be vibrating and an ophthalmologist suggested Olivia get an MRI.

Ahwatukee parents Kendra and Dave Riley take a stroll at their hotel with their three daughters, Eva, Olivia and Keira. The Rileys flew to Milan seeking gene therapy for Keira, who like Olivia was diagnosed with MLD.(Photo: Courtesy of Kendra Riley)

Two visits to two neurologists later, the Rileys learned Olivia had MLD.

Metachromatic leukodystrophy, or MLD, is a rare, hereditary disease that leads to premature death. It's characterized by the accumulation of fat in cells. The fat accumulation in nerve cells destroy white matter, an important tissue found in the brain and spinal cord that relays messages and affects learning functions.

Children must inherit a mutated gene from each parent to develop MLD. It's unknown how rare MLD is in the world; the incidence of MLD may range from 1 in 40,000 to 1 in 100,000, according to Cure MLD, a group that provides resources to families impacted by the disease.

The family tested their other two daughters, Eva, who is now 5, and Keira, who was 5 months old at the time. They received the results back in June: Eva is a carrier and Keira was diagnosed with MLD.

"Honestly, I feel like I had the same reaction for both," Kendra said. "An immediate feeling of being sick to your stomach, my entire body started shaking uncontrollably ... Its hard for one daughter to have this life-shortening disease. Two is too much for any parent in the world."

Olivia, who's in pain most days, has already lost the ability to talk, crawl and walk, Kendra said. In May, before transferring Olivia's treatment plan to Milan, the Rileys had begun a clinical trial in Iowa City with hopes of slowing down the disease's progression.

Through Cure MLD and the MLD Foundation, Kendra learned there was another possible option for Keira. Afairly new kind of gene therapy could potentially prolong herlife.

The catch: The therapy is only available at the San Raffaele Telethon Institute for Gene Therapy in Milan, the five-month stay including lodging and medical appointments would cost upwards of $500,000, and for the treatment to be most effective, Keira would need to start as soon as possible. With Italy banning nonessential travel from the U.S., the Rileys would need to secure passports and visas to allow them in.

FOR SUBSCRIBERS:His family inspired him to cook. Now they keep this Phoenix chef anchored during COVID

Friends, family, clients, government officials and strangers sprang into action.

A childhood friend in Yuma set up a bass fishing tournament as a fundraiser and netted around $6,000. Kendra's sister-in-law Nina Riley set up a GoFundMe that in a little more than a month, raised $243,517. Private donors pitched in the rest so the family could reach their $500,000 target.

Riley said she was amazed that even businesses that are struggling in the pandemic, such as Padre Murphy's sports bar in Glendale and Carlson Creek Vineyard, have been so supportive of her family.

"I feel like its something out of a movie, like it cant really be happening. Its not just about the donations. It's the messages Ive gotten, virtual hugs and prayers from complete strangers. All of it has restored our faith in humanity."

Through the coordinated efforts of the San Raffaele hospital, Arizona Rep. David Schweikert, the Consulate General of Italy in Los Angeles, the U.S. Postal Service and the Western Passport Center in Tucson, the Rileys were able to expedite the process of securing passports and medical visas for the entire family, plus Kendra's parents.

All of this was finalized the day before their flight to Italy, Kendra said with amazement.

Once they're back in the United States, Kendra and Dave plan to give back in some way to other families impacted by MLD. Kendra is in communication with Cure MLD to potentially work with the organization, which is described as a "global network of patient advocates and nonprofits." She and Dave are also considering starting their own foundation to support other families in situations like theirs.

"Hope is our biggest asset right now," Kendra said.

Reach the reporter at Priscilla.Totiya@azcentral.com. Follow @priscillatotiya on Twitter and Instagram.

Subscribe to azcentral.com today to support local journalism.

Read or Share this story: https://www.azcentral.com/story/entertainment/life/health/2020/09/05/how-community-helped-arizona-family-fight-daughters-rare-disease/5693441002/

Follow this link:
'Something out of a movie': How a community restored one family's 'faith in humanity' - The Arizona Republic

MINNEAPOLIS, Sept. 4, 2020 /PRNewswire/ -- Sickle Cell warrior Tahir "StayFresh" Ali of Atlanta, Ga., visits the hospital twice monthly for blood transfusions to reduce complications from sickle cell disease, and manage his potential risk of organ damage or stroke. The 35-year-old music producer and manager estimates he has spent several years of his life in the hospital undergoing treatment for sickle cell disease. Finding a perfectly matched marrow or blood stem cell donor could give StayFresh a chance to live life free of sickle cell and the many complications that the disease presents.

September is Sickle Cell Awareness Month, and Be The Match, the National Marrow Donor Program, is launching several campaigns to help people to learn more about the disease, and take action to help those searching for a matching blood stem cell or marrow donor.

StayFresh is like 100,000 African Americans who battle sickle cell disease, an often-misunderstood genetic disease that is "invisible" because unlike many illnesses, people with sickle cell disease can lead active lives. However, people with severe sickle cell can face debilitating episodes of pain crisis and life-threatening complications. StayFresh is working with Be The Match to rally more Black and African Americans to join the Be The Match Registry.

Be The Match is also hosting a three-part virtual event series to raise awareness about sickle cell disease, provide free resources for patients and families affected by sickle cell, discuss treatment options, and the need for more Black donors on the Be The Match Registry. The event series and more information can be found at: SickleCellConnect.com.

"We are grateful to have a dedicated Patient Services team that is able to produce these informative virtual events to help sickle cell patients and their caregivers learn how to access free resources and advocate for themselves as they navigate their disease," said Erica Jensen, Senior Vice President of Be The Match Member Engagement, Enrollment and Experience. "Nobody with sickle cell disease has to walk alone. Be The Match has a peer connect program, free professional counseling, nurse navigators and strong partnerships with organizations like The Sickle Cell Community Consortium and My Three Sicklers Foundation to ensure we can connect caregivers and sickle cell warriors with the resources they need to best manage this disease."

According to the Centers for Disease Control, sickle cell disease is the most common inherited disease, affecting 1 in 365 Black or African Americans and 1 in 16,300 Hispanic Americans. With sickle cell disease, oxygen-carrying red blood cells are misshapen, hard and sticky, which can result in them getting stuck in blood vessels and clog them. This can cause severe pain crisis, infections, organ damage, low blood counts, stroke and other serious health problems.

Be The Match has also launched an informative online video called "You Are My Match" to raise awareness of the need for more Black or African American donors on the Be The Match Registry to help Black patients battling sickle cell disease find a potentially life-saving match. The video features a 4-year-old girl named Ruby from Lubbock, TX, who has been hospitalized more than 24 times and had three surgeries due to her sickle cell. Ruby's doctors are recommending a blood stem cell or marrow transplant due to the severity of her condition, but she does not have a perfect match on the Be The Match Registry.

Part of the challenge Black patients like Ruby face when searching for a perfect match is low representation of Black or African Americans on the Be The Match Registry. Of the 22 million potential donors on the Be The Match Registry, just 4 percent are Black or African American. Because ethnicity plays a role in finding a match, Black patients will only find a perfect match 23% of the time, which is much lower than other ethnicities, such as White patients, who will find a match 77% of the time.

To learn how to access free resources, read stories about people cured of sickle cell disease following a marrow or stem cell transplant and to join the Be The Match Registry, visit: http://www.sicklecellconnect.com.

Virtual Event Series:Episodes will be streamed via http://www.sicklecellconnect.comwebpage and viewable on Be The Match Social Channels.

Episode 1: What is sickle cell disease?September 10thfrom 12:00 12:30 p.m. CDTWe'll chat about sickle cell disease basics with pediatric hematologist Staci Arnold, MD, hear sickle cell warrior Genesis' storyandlearn about barriers and disparities that sickle cell patients face from the Health Equity Manager at Be The Match.

Episode 2: Living with sickle cell diseaseSeptember 17th from 12:00 12:30 p.m. CDTWe'll chat with a Be The Match Patient Navigator and Social Worker about the free resources available to sickle cell disease patients and hear from the founder of My Three Sicklers Foundation.

Episode 3:The future of sickle cell diseaseSeptember24th from 12:00 1:00p.m. CDTWe'll cover transplant and gene therapy with Staci Arnold, MD and a certified genetic counselor from BeTheMatch. Hear about our policy efforts for sickle cell disease, meet sickle cell warriorDakhiyon, seehow Nia Imani Franklin, former Miss America, is advocating for more diverse donors on the Be The Match Registry, plus watch a live swabbing event!

SOURCE Be The Match

https://www.sicklecellconnect.com

See the original post:
Be The Match Presents "Sickle Cell Connect" Virtual Event Series To Raise Awareness Of Treatment Options And Marrow Transplants As A Cure...

Local medtech companies are stepping up to fight COVID-19 and changing the way they work in the process.

Thats what Spark Therapeutics Kristin Kahle, Ph. D told Technical.lyreporter Paige Gross during an Amplify Philly @ Home fireside chat last week, when thetwo discussed the role Philadelphias medtech community is playing in helping find a cure for COVID-19 and how Kahles professional journey has led to her current position.

In her role as immunomonitoring lead at Spark, which last year was acquired by Roche in a $4.8 billion deal (Phillys biggest-ever VC-backed exit), Kahle and her team study gene therapy for people with genetic disorders.

Gene therapy has been so rewarding for me, she said. There is so much to learn there that I am quite happy to contribute to that. Gene therapy is the silver bullet to many diseases that dont have cures.

Kahle earned her Ph.D. from Jefferson University, where she studied HIV and fusion inhibitors. She later worked at biotech firms Invisible Sentinel andIntegral Molecular before her current appointment at Spark.

Adapting to COVID-19 was a huge shift for Kahle and her team, but it was one that she said they have managed effectively so far.

At Spark, when the pandemic hit, our first concern was safety of our employees and people in our trials, she said. We had to stop enrollment in clinical trials and that was a little bit like letting air out of the balloon. But it was the right decision to not potentially expose patients to the healthcare system and not potentially strain the healthcare system.

In trying to adjust to a pandemic, Spark reexamined its objectives to see how employees could remain productive while prioritizing their health and safety. Kahle said Spark is now in a restart phase and its laboratories are at between 50 to 60% of their usual occupancy.

In addition to adapting internally, Kahle said that Spark and other medtech companies wanted to help the community fight the spread of COVID-19. One way of doing that was by Spark donating as much PPE as it could to hospitals and essential workers.

Kahle is optimistic about the work local medtech professionals are doing in fighting COVID-19 and shouted out her former employer Integral Moleculars recent work as an example: The company mapped out the receptors that COVID-19 uses to get into human cells and was awarded $1 million from the National Institute of Allergy and Infectious Diseases to support its work.

Local medtech firms are also collaborating to find a cure for COVID-19, a move that Kahle said underscored the gravity of the pandemic.

Depending on your companys mission, it may go back to a competitor type of relationship [after COVID-19], she said. Companies are very protective of their intellectual property, but it takes something this devastating to people around the world to bring people together.

Since first entering the medtech industry, Kahle has noticed significant growth and development at companies in Philadelphia that wasnt happening when she began her career. She considers that growth along with resources like the citys universities and institutions such as the University City Science Center to be positive indicators of Phillys future success in medtech.

I think Philly may be overlooked, but it really is a medtech ecosystem, she said. [Professionals] stay here because they love the city and companies want to be a part of that. I also think that theres a lot of opportunities to build state-of-the-art facilities here. There are a ton of opportunities and talented scientists.

Watch a recording of the fireside chat below, starting at the 1:26:53 mark:

Original post:
Philly's medtech companies are working together to fight COVID-19 - Technical.ly

One of the major challenges facing gene therapy - a way to treat disease by replacing a patients defective genes with healthy ones - is that it is difficult to safely deliver therapeutic genes to patients without the immune system destroying the gene, and the vehicle carrying it, which can trigger life-threatening widespread inflammation.

Three decades ago researchers thought that gene therapy would be the ultimate treatment for genetically inherited diseases like hemophilia, sickle cell anemia and genetic diseases of metabolism. But the technology couldnt dodge the immune response.

Since then, researchers have been looking for ways to perfect the technology and control immune responses to the gene or the vehicle. However, many of the strategies tested so far have not been completely successful in overcoming this hurdle.

Drugs that suppress the whole immune system, such as steroids, have been used to dampen the immune response when administering gene therapy. But its difficult to control when and where steroids work in the body, and they create unwanted side effects. My colleague Mo Ebrahimkhani and I wanted to tackle gene therapy with immune-suppressing tools that were easier to control.

I am a medical doctor and synthetic biologist interested in gene therapy because six years ago my father was diagnosed with pancreatic cancer. Pancreatic cancer is one of the deadliest forms of cancer, and the current available therapeutics usually fail to save patients. As a result, novel treatments such as gene therapy might be the only hope.

Yet, many gene therapies fail because patients either already have pre-existing immunity to the vehicle used to introduce the gene or develop one in the course of therapy. This problem has plagued the field for decades, preventing the widespread application of the technology.

Traditionally scientists use viruses - from which dangerous disease-causing genes have been removed - as vehicles to transport new genes to specific organs. These genes then produce a product that can compensate for the faulty genes that are inherited genetically. This is how gene therapy works.

Though there have been examples showing that gene therapy was helpful in some genetic diseases, they are still not perfect. Sometimes, a faulty gene is so big that you cant simply fit the healthy replacement in the viruses commonly used in gene therapy.

Another problem is that when the immune system sees a virus, it assumes that it is a disease-causing pathogen and launches an attack to fight it off by producing antibodies and immune response just as happens when people catch any other infectious viruses, like SARS-CoV-2 or the common cold.

Recently, though, with the rise of a gene editing technology called CRISPR, scientists can do gene therapy differently.

CRISPR can be used in many ways. In its primary role, it acts like a genetic surgeon with a sharp scalpel, enabling scientists to find a genetic defect and correct it within the native genome in desired cells of the organism. It can also repair more than one gene at a time.

Scientists can also use CRISPR to turn off a gene for a short period of time and then turn it back on, or vice versa, without permanently changing the letters of DNA that makes up or genome. This means that researchers like me can leverage CRISPR technology to revolutionize gene therapies in the coming decades.

But to use CRISPR for either of these functions, it still needs to be packaged into a virus to get it into the body. So some challenges, such as preventing the immune response to the gene therapy viruses, still need to be solved for CRISPR-based gene therapies.

Being trained as a synthetic biologist, I teamed up with Ebrahimkhani to use CRISPR to test whether we could shut down a gene that is responsible for immune response that destroys the gene therapy viruses. Then we investigated whether lowering the activity of the gene, and dulling the immune response, would allow the gene therapy viruses to be more effective.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

A gene called Myd88 is a key gene in the immune system and controls the response to bacteria and viruses, including the common gene therapy viruses. We decided to temporarily turn off this gene in the whole body of lab animals.

We injected animals with a collection of the CRISPR molecules that targeted the Myd88 gene and looked to see whether this reduced the quantity of antibodies that were produced to specifically fight our gene therapy viruses. We were excited to see that the animals that received our treatment using CRISPR produced less antibody against the virus.

This prompted us to ask what happens if we give the animal a second dose of the gene therapy virus. Usually the immune response against a gene therapy virus prevents the therapy from being administered multiple times. Thats because after the first dose, the immune system has seen the virus, and on the second dose, antibodies swiftly attack and destroy the virus before it can deliver its cargo.

We saw that animals receiving more than one dose did not show an increase in antibodies against the virus. And, in some cases, the effect of gene therapy improved compared with the animals in which we had not paused the Myd88 gene.

We also did a number of other experiments that proved that tweaking the Myd88 gene can be useful in fighting off other sources of inflammation. That could be useful in diseases like sepsis and even COVID-19.

While we are now beginning to improve this strategy in terms of controlling the activity of the Myd88 gene. Our results, now published in Nature Cell Biology,provide a path forward to program our immune system during gene therapies and other inflammatory responses using the CRISPR technology.

See the original post here:
CRISPR can help combat the troubling immune response against gene therapy - The Conversation US

Paula Cannon. (USC Photo/Richard Carrasco)

An HIV research program led by scientists at USC and the Fred Hutchinson Cancer Research Center in Seattle has received a five-year, $14.6million grant from the National Institutes of Health. The team is advancing a gene therapy approach to control the virus without the need for daily medicines.

The programs co-directors are Paula Cannon, PhD, Distinguished Professor of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, and Hans-Peter Kiem, MD, PhD, the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutch. Other key partners are David Scadden, MD, a professor at Harvard University, and the biotechnology company Magenta Therapeutics.

The NIH award will support preclinical studies that combine gene editing against HIV with technologies for safer and more effective hematopoietic stem cell transplants. Such transplants, also known as bone marrow transplants, are currently used for severe blood cancers. They renew a patients immune system, which can be damaged by cancer therapies, by infusing healthy donor blood stem cells that can grow into any type of blood or immune cell.

The researchers goal is to build a therapy that prepares patients for a stem cell transplantation using their own cells with little to no toxicity, engineers their own stem cells to fight HIV and stimulates those cells to quickly produce new and engineered immune cells once theyre reintroduced into the patient.

This grant funds a team with an overarching goal of developing what our perfect HIV gene therapy would look like, Cannon said. All of these pieces could happen separately, but the fact that the NIH has funded us as a team means that the sum will be so much bigger than the parts.

Halting HIV without daily drugs

About 38million people worldwide are living with HIV, the virus that causes AIDS. HIV is manageable with daily antiretroviral drugs, but the research team seeks a more durable solution.

Their strategy is inspired by the three cases where patients seem to have been cured of HIV. All had aggressive leukemia and received blood stem cell transplants from donors who also carried a mutation that confers immunity to HIV. The mutation was in the CCR5 gene, which encodes a receptor that HIV uses to infect immune cells and is present in about 1 percent of the population.

Timothy Ray Brown, famously nicknamed the Berlin patient, received such a transplant in 2007; he has been off antiretroviral drugs since then, and the virus remains undetectable in his system. In recent years, patients in London and Dusseldorf have shown similar results.

I think of the Berlin patient as proof of principle that replacing the immune system with one thats HIV-resistant by removing CCR5 is a possible way to treat somebody, Cannon said.

However, the rigors of the blood stem cell transplant process, combined with the difficulty in finding tissue-matched CCR5-negative donors, make it highly unlikely that this will provide more than a very rare treatment.

Three for one gene therapy

The research team will tackle these two major problems. First, to get around the lack of CCR5-negative donors, Cannon has already helped pioneer the use of gene editing to remove CCR5 from a patients own stem cells. This is now an investigational treatment for HIV in a clinical trial at City of Hope in Duarte, California.

She will now combine CCR5 disruption with additional genetic changes, so that the progeny of engineered stem cells will release antibodies and antibody-like molecules that block HIV.

Our engineered cells will be good neighbors, Cannon said. They secrete these protective molecules so that other cells, even if they arent engineered to be CCR5-negative, have some chance of being protected.

Meanwhile, Kiems group is providing a third approach by adapting an emerging cancer treatment called CAR T cell therapy. This re-engineers T cells of the immune system with chimeric antigen receptors (CARs), which are customized to recognize cancer cells.

In this project, Kiem and colleagues will create stem cells whose T cell descendants can instead hunt down HIV-infected cells.

A gentler blood stem cell transplant

The grant also supports two other components that relate to the blood stem cell transplant.

Magenta Therapeutics is developing less-toxic protocols for conditioningpreparing a patients bone marrow to receive a transplant. Traditionally, mild chemotherapy or radiotherapy is needed to make room for newly infused stem cells and to help them re-engraft.

The company is instead using antibody-drug conjugates to deliver this conditioning much more narrowly and to reduce the side effects that occur with systemic chemo or radiation.

Meanwhile, Scadden and his team are addressing another drawback of stem cell transplants and conditioning, the delay before infused stem cells generate new immune cells in sufficient numbers. In cancer patients, this delay leaves them highly susceptible to infection.

Scadden is approaching this using an injectable gel that biochemically resembles the bone marrow environment, to quickly repopulate the immune system with HIV-fighting cells.

With success, the teams research may free HIV patients from the need for daily medication and the expense and potential side effects that come with it. Their work may also improve other therapies based on blood stem cells, for conditions such as cancer, sickle cell disease and autoimmune disorders.

A home run would be that we completely cure people of HIV, Cannon said. What Id be fine with is the idea that somebody no longer needs to take anti-HIV drugs every day because their immune system is keeping the virus under control, so that it no longer causes health problems and, importantly, they cant transmit it to anybody else.

By Wayne Lewis

Read the original:
Gene therapy research for HIV awarded $14.6 million NIH grant - USC News

The company is to invest 3.4m (around US$4.5m) alongside the grant.

The funds will support research into the manufacturing challenges associated with scaling gene therapies for widespread patient access, to further develop technologies to improve the safety and efficacy of current therapies, and to enable the treatment of genetic diseases with more complicated disease pathways the industry is not yet able to address.

Along with the creation of 11 new jobs in Edinburgh, the developer said it will further enhance its Pro10 platform, an AAV manufacturing process that can be scaled and applied throughout the group.

The grant will also advance development of the tool kit of inducible, repressible, tunable and responsive expression cassettes to be adopted in the current clinical pipeline and new disease targets.

Gene therapy has the potential to treat a wide range of diseases including certain forms of muscular dystrophy, congestive heart failure and some diseases of the central nervous system but, at present, only two market-approved therapies are available.

David Venables, president, AskBio Europe, commented: The grant awarded by Scottish Enterprise supports AskBio in working towards developing even safer and more effective gene therapies through improved development and manufacturing techniques. Science and innovation keep progressing, and that makes this an exciting time to develop this type of therapeutic agent.

AskBios technology is inside both currently approved AAV gene therapies, which include Luxturna, developed by Spark Therapeutics, for the treatment of patients with inherited retinal disease, and Zolgensma, developed by AveXis, for the treatment of patients with spinal muscular atrophy (SMA).

AveXis licenses AskBios self-complementary DNA technology for Zolgensma.

While the promise of such therapies is being shown, significant barriers remain before gene therapies can become more broadly impactful, according to AskBio.

With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, UK, AskBio has generated hundreds of proprietary third generation AAV capsids and promoters, several of which have entered clinical testing.

BioPharma-Reporter (BPR) spoke to Ken Macnamara, (KM), PhD, chief operating officer, AskBio Europe,to get the AAV developers take on the factors preventing gene therapy going mainstream.

BPR: What criteria did AskBio have to fulfill to be awarded this grant?

KM: The research must be highly novel with significant risk from which a successful outcome will accelerate business growth within Scotland and globally.

BPR: What are the current manufacturing challenges associated with scaling gene therapies for widespread patient access?

KM: As we see growing evidence that gene therapy is a viable, transformational medicine, along with an acceleration in the number of AAV therapeutics moving towards regulatory approval, the ability to manufacture these therapies for diseases with large patient populations does not exist today and costs are extremely high.

Many companies can manufacture small batches of therapeutics for clinical applications, but as they approach commercialization, the challenges of production costs and timelines remain an issue. We recognized this more than a decade ago and focused on creating robust, scalable manufacturing capabilities.

Today, the challenges for manufacturing gene therapy are being met by simply adding large amounts of capacity, which is not the long-term answer. There is a significant amount of innovation taking place that will no doubt shape the future of manufacturing AAV gene therapeutics. This work continues today in our Edinburgh and US facilities to further improve the technology.

BPR: What are some of the typical safety and efficacy issues linked to current therapies?

KM: Currently approved gene therapies have provided effective therapy by targeting tissues in the body with an administered gene that produces a new, effective protein. This new gene replaces the defective or missing gene causing the patients underlying disease.

Because the techniques are relatively new, some of the risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible.

AAV is not known to cause human disease, and it cannot make more of itself without outside help, so it will not replicate in the body like normal viruses do. AAV is engineered to carry therapeutic genes by removing some of its genetic cargo and replacing it with human gene sequences. This results in an AAV vector, a therapeutic genetic medicine.

Risks associated with AAV gene therapy vector administration include unwanted immune system reactions. The body's immune system may see the newly introduced AAV vectors as intruders and attack them, which may cause inflammation and, in severe cases could be local and mild or throughout a greater area of the body and be more serious. AAV vectors can also target tissues other than the intended tissue. Thus, it's possible that AAV vectors may affect additional cells, not just the targeted cells containing mutated genes. These are called off-target effects. If this happens, healthy cells may be damaged.

BPR: Can you indicate the other significant barriers that remain before gene therapies can become more broadly impactful?

KM: Therapies need to express the gene in the right tissue, at the right level, for the right amount of time. There is a great deal of research happening throughout the gene therapy field to identify the best means of delivering and controlling activation of the genetic material. Furthermore, the response of the patients immune system also needs to be considered based on the therapy. Additional funding, like that from Scottish Enterprise, can help speed up the development process of promising therapies.

BPR: How does AskBio envisage exploring the treatment of genetic diseases with more complicated disease pathways that the industry is not yet able to address?

KM: One of the most exciting advances in modern medicine has been the discovery of how AAV vectors can be used as an effective delivery system for therapeutic genetic material into living tissue. AAV gene therapy has broad therapeutic implications for a vast array of diseases.

Some genetic diseases are caused by mutations in a single gene, while others are a result of mutations in multiple genes, for example, cancer. Additionally, environmental factors, such as smoking and diet, can play a role in diseases. The complexity of these disease characteristics creates variables in developing and testing potential treatments. Currently the gene and cell therapy options that exist today are limited to treating diseases caused by a single gene mutation.

AskBios Edinburgh team leads the gene therapy field in the design and development of synthetic gene expression cassettes. The technology is essential for controlling the expression of AAV therapeutics, thereby improving their safety and efficacy. This R&D project will enable AAV therapeutics to be turned on and off and dialed up or down depending on the amount of drug needed at any given time. This technology provides a desired safety switch and level of variable dosing that previously did not exist. Before this breakthrough, AAV therapeutics could only express at one constant level and could not be turned off, which limited the type of therapeutics for which AAV could be used and may hold the key to treating pathway diseases where multiple genes are affected.

BPR: On the job creation front, is the talent already hired or are you starting a recruitment drive?

KM: The grant allows us to make some positions permanent and bring in new talent.

Ken Macnamara joined AskBio in 2019 with a wealth of R&D, business operations, financial planning, intellectual property and quality/compliance experience gained from start-up to multinational firms. He most recently was COO at Synpromics.

Dr Macnamara began his career at the University of Edinburgh, where he earned a PhD in chemistry before helping to start Lab901 (Scottish SME). There, he was a product development manager responsible for developing the TapeStation and ScreenTape technologies from concept to market success. Lab901 was acquired by Agilent Technologies in 2011. Dr Macnamara then served as R&D director for the Microfluidics business at Agilent.

View post:
Reducing barriers to mainstream gene therapy - BioPharma-Reporter.com