Category Archives: Gene Medicine

Researchers have been experimenting with different ways to deliver genes to the brain to treat central nervous system diseases and tumors. One of the obstacles, however, is the ability to penetrate the blood-brain barrier while having minimal effect on the other organs in the body.

Hong Chen, associate professor of biomedical engineering at the McKelvey School of Engineering and of radiation oncology at the School of Medicine, both at Washington University in St. Louis, and her team found an effective method to overcome that obstacle using focused ultrasound intranasal delivery (FUSIN). In new research, they found that the intranasally delivered gene therapy had comparable or better outcomes than existing methods while having minimal effect on the bodys other organs.

Results of the research, led by Chen and Dezhuang Ye, a postdoctoral research associate, and collaborators, were published online in the journal eBioMedicineSept. 21. It is the first study to evaluate the potential of FUSIN to deliver adeno-associated viral vectors, small viruses used to deliver gene therapy, in a mouse model.

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A sound approach for effective gene therapy delivery to brain - The Source - Washington University in St. Louis - Washington University in St. Louis

CARLSBAD, Calif.--(BUSINESS WIRE)--Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, announced today that Brian M. Culley, Lineages Chief Executive Officer, will present at the Alliance for Regenerative Medicine 2022 Cell & Gene Meeting on the Mesa, on October 12th, 2022 at 2:15pm PT / 5:15pm ET at the Park Hyatt Aviara, Carlsbad, CA. Virtual meeting attendance is available and includes a livestream of Lineages presentation and the ability to view all conference sessions on-demand. Interested parties can visit the 2022 Cell & Gene Meeting on the Mesa website for full information on the conference, including registration.

The Cell & Gene Meeting on the Mesa is the sectors foremost annual conference bringing together senior executives and top decision-makers in the industry to advance cutting-edge research into cures. Tackling the commercialization hurdles facing the cell and gene therapy sector today, this meeting covers a wide range of topics from clinical trial design to alternative payment models to scale-up and supply chain platforms for advanced therapies. The program features expert-led panels, extensive partnering capabilities, exclusive networking opportunities, and dedicated presentations by the leading publicly traded and privately held companies in the space. This conference enables key partnerships through more than 3,000 one-on-one meetings while highlighting the significant clinical and commercial progress in the field.

About the Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is the leading international advocacy organization dedicated to realizing the promise of regenerative medicines and advanced therapies. ARM promotes legislative, regulatory, reimbursement and manufacturing initiatives to advance this innovative and transformative sector, which includes cell therapies, gene therapies and tissue-engineered therapies. In its 13-year history, ARM has become the global voice of the sector, representing the interests of 450+ members worldwide, including small and large companies, academic research institutions, major medical centers and patient groups.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include five allogeneic (off-the-shelf) product candidates: (i) OpRegen, a retinal pigment epithelial cell therapy in development for the treatment of geographic atrophy secondary to age-related macular degeneration, is being developed under a worldwide collaboration with Roche and Genentech, a member of the Roche Group; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; (iii) VAC2, a dendritic cell therapy produced from Lineages VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer; (iv) ANP1, an auditory neuronal progenitor cell therapy for the potential treatment of auditory neuropathy; and (v) PNC1, a photoreceptor neural cell therapy for the treatment of vision loss due to photoreceptor dysfunction or damage. For more information, please visit http://www.lineagecell.com or follow the company on Twitter @LineageCell.

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Lineage to Present at Alliance for Regenerative Medicine 2022 Cell & Gene Meeting on the Mesa - Business Wire

(Aylish Turner | Daily Trojan)

A mutation in a newly discovered microprotein might lead to a significant risk for Alzheimers disease, according to research from the Leonard Davis School of Gerontology. The discovery expanded the gene target to treat the disease and provided a new potential therapeutic solution to the incurable disease.

The newly-discovered protein, named SHMOOSE, is encoded by a gene that exists within the cells mitochondria, which is responsible for cells energy production. A mutation within this gene, which partially inactivates the SHMOOSE microprotein, is associated with a 30% increase in ones risk of developing Alzheimers disease. The mutated version of the protein has reportedly appeared within nearly a quarter of people of European ancestry.

Brendan Miller, a 2022 doctoral graduate who studied neuroscience and the studys first author, relied on big data techniques to identify genetic variations associated with disease risk, after analyses revealed that mutations are linked to increased risk of Alzheimers, brain atrophy and energy metabolism.

Researchers began studying the genes mutated and default forms and found that SHMOOSE is the first mitochondrial-DNA-encoded microprotein to be detected using both antibodies and mass spectrometry.

Miller said one of the biggest obstacles in the research process was the sheer amount of data that researchers had to compile to make these findings. Miller described this big data as taking up terabytes of storage, containing research gleaned from dozens of individuals. His team was able to overcome this by utilizing new and advanced technology, which allowed them to make discoveries not otherwise possible.

Computational power over the last ten years has grown exponentially. With that means youre going to see in the field of medicine and biology a lot of rapid discoveries, Miller said. At USC, we have infrastructure, and we have a lot of talented computational scientists to help us with that.

Being able to manipulate and understand big data was essential for the success of this project, Miller said.

The big challenge is starting from hundreds of potential gene targets and narrowing them down to one, Miller said. The way we did this was [by] implementing a lot of genetics data and omics data from similar individuals with different data types.

The study highlights the importance of the emerging field of microprotein studies. Microprotein, a small protein encoded from a small open reading frame, appears to modify energy signaling and metabolism in the central nervous system. A variety of studies have found microproteins in mitochondria of neurons and showed that SHMOOSE alters energy metabolism in the brain, in part by inhibiting the inner mitochondrial membrane.

When you look at microproteins, there are many hundreds of thousands of them, [which] creates a whole new dimension of things that need to be discovered, said Pinchas Cohen, a professor of gerontology, medicine and biological sciences and the senior author of the study.

There is currently no approved medicine for Alzheimers disease developed based on microproteins, while microprotein- or peptide-related treatments have been employed in treatments of diabetes, heart diseases and some other chronic illnesses. The therapeutic potential of microproteins in Alzheimers cases was thus exciting news for many researchers in the field.

Helena Chang Chui, chair and professor of neurology at Keck School of Medicine, said the paper is very rich and has significant potential impact for understanding the causes of Alzheimers.

Were getting a little bit closer with immunological approaches with monoclonal antibodies[and] antibodies against amyloid proteins, but theres been no particular no peptide treatments, Chui said.

Researchers are, on the whole, cautiously optimistic about the therapeutic potential of the study, Cohen said, and it is still too early to contemplate applying the findings of the study into therapeutic research. Cohen said he hopes that the team could use standard mouse models of Alzheimers and demonstrate that SHMOOSE does have benefits on the treatment of Alzheimers disease.

Then, as Cohen implied, the team might pick individuals who have the SHMOOSE mutation to do the research, which will lend to the precision medicine approaches.

The issue is that Alzhmeimers disease is very heterogeneous. [Its] not really one specific condition, its multiple conditions, each being a result of various genetic susceptibilities, that all present in a similar way, Cohen said. Thats why I believe that treatments that will be focused on the primary genetic abnormality, also known as precision medicine approaches, will be more efficacious.

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Study finds microprotein correlated to Alzheimers risk - Daily Trojan Online

Risky at-birth surgery saves baby with rare disorder

Doctors have performed a dramatic surgery to save a baby who was born with a life-threatening rare disorder that hampered his ability to breathe. (Sept. 21) (AP Video: Emma H. Tobin)

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Every baby born in the United States is pricked in the heel shortly after birth. A blood sample is then analyzed to look for one of 20 to 30 inherited diseases.

Early identification of a particular disease meanstreatment can start right away, potentially saving or extending thechild's life.

Now, doctors want to go even further: They want to look not just atblood, but atgenes.

A new effort announced Wednesday by a genetic testing company paired withresearchers at NewYork-Presbyterian/Columbia Universityaims to sequence 100,000 newborns in New York City over the next five years.

The sequencing would look for about 250 diseases that strike before age 5 and for which there are treatments or approaches that can make a difference in a child's life.

A similar effort in the United Kingdom is also examining the genes of 100,000 newborns, looking for diseases for which there is a treatment or a cure.

The programs promiseto bring treatments to babies before symptoms become obvious and at a time when something can be done to help them.

"The appetite for this is growing. The awareness of this is growing. We all see it as inevitable," said Dr. Robert Green, a medical geneticist atBrighamand Women's Hospital and Harvard Medical School, both in Boston."We are grossly underutilizing the life-saving benefits of genetics and we have to get past that."

This week,Green is hosting a conference in Boston, bringing together researchers and industry representatives from the U.S., U.K., European Union and Australia to set standards and discuss the challenges and opportunities presented byscaling upnewborn genetic sequencing.

This kind of early sequencing and treatment is possible now for the first time because of dramatic advances in diagnostics, therapies and digital data storage, as well as a reduction in the cost of sequencing, said Dr. Paul Kruszka, a clinical geneticist and chief medical officer of GeneDx at Sema4, which is leading the new program.

"We're entering the therapeutic era and leaving the diagnostic era," Kruszka said. "This potentially has the opportunity to change the way we practice medicine especially in rare disease."

Right now, families with rare diseases often search for a diagnosis for 5, 10 or even 20 years. If the child could be diagnosed at birth, he said, it would short-circuit that process and treatment could begin much earlier hopefully before the child suffers irreversible damage.

Before deciding whether every family should get access to genetic sequencing for their newborn,large studies like Sema4's are needed to justify the cost, Kruszka said.

The price of gene sequencing has dropped precipitiously, with one company, Illumina. announcing last week that its newest-generation sequencing machinescan run a complete sequence for about $200. Kruszka said Sema4 expects to still payabout $1,000 for each sequence of all 20,000 genes.

Gene sequencing at birth should be able to save money over the child's lifetime by preventing illness, Green said. The costs of sequencing are limited, he said, but the benefits will build up over the child's lifetime and may help family members, too.

Green and his team began analyzing the genetic sequences of newborns in 2013, and has found lots of useful information among the first 320 babies sequenced, he said. He now has funding to expand his sequencing researchto 1,000 newborns.

Large numbers are essential because most of the diseases being diagnosed are extremely rare.

Convincing parents to participate in a sequencing research trial "is not easy," Green said. Many are concerned about privacy and the discrimination their child might face if their genome were made public. And it can be a unpleasant for parents to consider the horrible diseases their perfect newborn might be harboring,he said.

"You've gone through all this pregancy and you're sitting there with a healthy baby (and I'm) offering you the opportunity to find out something that's devastating and terrifying," he said. "How fun is that?"

He doesn't think privacy needs to be a major parental concern. Companies can learn more useful information by tracking someone's cell phone or credit card than their genome and most common diseases are the result of many combinations of genes.

"Many people hear 'genetics' and worry somehow that that is a special kind of privacy threat," he said, adding that he doesn't think there is. "We haven't been paying attention to the medical benefits of genetic testing, particularly predictive genetic testing."

if people don't want to know, that's okay, too, Green said. "We canrespect people who don't want to know, but as also respect people who do want to know," he said. "Some families will say 'I treasure the precious ignorance.' Others will say 'If I could have known, I would have poured my heart and soul into clinical trials or spent more time with the child when she was healthy."

In a five-year review of their research, Green and his colleagues found that "terrible things didn't happen" when they sequenced newborn genomes.

Families, he said, "did not in fact have downstream distress," he said. "They did have appropriate medical follow-up and that there were amazing benefits to the babies and the families as a result of the surveillance and treatment."

The baby sequencing identified several parents who had inherited illnesses and received risk-reducing surgery, he said, as well as a baby who had a narrowed aorta that wouldn't have been detected if its genetics hadn't indicated the need for an echocardiogram.

"Even in a small sample we found much to act on," he said.

At Rady Children's Hospital in San Diego, they're trying to rapidly sequence the genomes of babies who already have problems and are being treated in one of 83 children's hospitals acrossCanada and the U.S.

Every morning, samples arrive by Fedex. In some cases, the baby is in such dire shape than an answer is needed immediately. For those children, "we've got to drop what we're doing and go,"said Dr. Stephen Kingsmore, the president and CEO of Rady's Institute for Genomic Medicine."Even a day can cost a child's life or brain function."

For babies who are stable, sequencing still happens rapidly, but a little less so."Every sample gets onto a sequencer the same day," he said.

So far, the institute, which is also collaborating on a newborn sequencing study in Greece,has been able to provide a 1,500 children with a diagnosis in the first weeks of life in addition to a life-saving treatment.

"That idea, that future is where a child never experiences a sick day, even though they have a fatal condition," the institute's former director of marketing,Graciela Sevilla,said earlier this year. "We'd love to see that on a regular basis."

Contact Weintraub at kweintraub@usatoday.com

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

Air pollution could be contributing to millions of premature births

Estimates in a new study say air pollution could be a factor in up to 3.4 million preterm births.Video provided by Newsy

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Blood from a baby at birth can be gene sequenced to prevent diseases - USA TODAY

Passage Bio

PHILADELPHIA, Oct. 10, 2022 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders, today announced the appointment of William Chou, M.D. as chief executive officer (CEO) and a member of the board, effective immediately. Edgar B. (Chip) Cale will resign his position as the companys interim CEO and will continue in his role as general counsel and corporate secretary. Maxine Gowen, Ph.D., will step down as interim executive chairwoman following a brief transition period and will then continue to serve as chairwoman.

The Board and I are delighted to welcome Will to Passage Bio to lead the company through an exciting phase of development, said Dr. Gowen. Wills depth of experience and success in developing and commercializing advanced therapeutics will be instrumental in establishing and solidifying the company as a leader in genetic medicines.

Dr. Chou is an accomplished executive with nearly twenty years of healthcare experience across a range of development and commercialization roles. Most recently, Dr. Chou served as CEO of Aruvant Sciences, a clinical-stage biopharmaceutical company focused on developing gene therapies for rare diseases.

I am thrilled to join the talented team at Passage Bio and build upon the companys many accomplishments and impressive capabilities, said Dr. Chou. With three ongoing clinical programs, we are poised to deliver multiple meaningful milestones over the coming quarters. As a clinician, it is my privilege to lead a company with tremendous potential to bring transformative therapies to patients with CNS disorders for which there are limited or no approved treatment options today.

Prior to joining Aruvant, Dr. Chou served in a variety of leadership roles at Novartis, including vice president, global disease lead for Novartis Cell and Gene Therapy unit where he oversaw the global commercial launch of Kymriah, the first CAR-T cell therapy. Prior to that role, Dr. Chou led the Kymriah lymphoma clinical development program to approvals in the United States, Europe, Australia, Canada and Japan. Before joining Novartis, Dr. Chou worked at the Boston Consulting Group where he focused on commercial and clinical pharmaceutical strategy.

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Dr. Chou holds an M.B.A. from the Yale School of Management, an M.D. from the University of Pittsburgh School of Medicine, and an A.B. in politics and economics from Princeton University. Dr. Chou completed his residency in internal medicine at Yale New Haven Hospital and his fellowship in geriatrics at Yale University.

About Passage Bio

Passage Bio (Nasdaq: PASG) is a clinical-stage genetic medicines company on a mission to provide life-transforming therapies for patients with CNS diseases with limited or no approved treatment options. Our portfolio spans pediatric and adult CNS indications, and we are currently advancing three clinical programs in GM1 gangliosidosis, Krabbe disease, and frontotemporal dementia with several additional programs in preclinical development. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvanias Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. Through this collaboration, we have enhanced access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at http://www.passagebio.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Passage Bio Investors:Stuart HendersonPassage Bio267-866-0114shenderson@passagebio.com

Passage Bio Media:Mike BeyerSam Brown Inc. Healthcare Communications312-961-2502MikeBeyer@sambrown.com

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Passage Bio Announces Appointment of William Chou, M.D. as Chief Executive Officer - Yahoo Finance

Newswise PHILADELPHIAAdults with a genetic form of childhood-onset blindness experienced striking recoveries of night vision within days of receiving an experimental gene therapy, according to researchers at the Scheie Eye Institute in the Perelman School of Medicine at the University of Pennsylvania.

The patients had Leber Congenital Amaurosis (LCA), a congenital blindness caused by mutations in the gene GUCY2D. The researchers, whose findings are reported in the journal iScience, delivered AAV gene therapy, which carries the DNA of the healthy version of the gene, into the retina of one eye for each of the patients in accordance with the clinical trial protocol. Within days of being treated, each patient showed large increases, in the treated eye, of visual functions mediated by rod-type photoreceptor cells. Rod cells are extremely sensitive to light and account for most of the human capacity for low-light vision.

These exciting results demonstrate that the basic molecular machinery of phototransduction remains largely intact in some cases of LCA, and thus can be amenable to gene therapy even after decades of blindness, said study lead author Samuel G. Jacobson, MD, PhD, a professor of Ophthalmology at Penn.

LCA is one of the most common congenital blindness conditions, affecting roughly one in 40,000 newborns. The degree of vision loss can vary from one LCA patient to another but all such patients have severe visual disability from the earliest months of life. There are more than two dozen genes whose dysfunction can cause LCA.

Up to 20 percent of LCA cases are caused by mutations in GUCY2D, a gene that encodes a key protein needed in retinal photoreceptor cells for the phototransduction cascadethe process that converts light to neuronal signals. Prior imaging studies have shown that patients with this form of LCA tend to have relatively preserved photoreceptor cells, especially in rod-rich areas, hinting that rod-based phototransduction could work again if functional GUCY2D were present. Early results with low doses of the gene therapy, reported last year, were consistent with this idea.

The researchers used higher doses of the gene therapy in two patients, a 19- year-old man and a 32-year-old woman, who had particularly severe rod-based visual deficits. In daylight, the patients had some, albeit greatly impaired, visual function, but at night they were effectively blind, with light sensitivity on the order of 10,000 to 100,000 times less than normal.

The researchers administered the therapy to just one eye in each patient, so the treated eye could be compared to the untreated eye to gauge treatment effects. The retinal surgery was performed by Allen C. Ho, MD, a professor of Ophthalmology at Thomas Jefferson University and Wills Eye Hospital. Tests revealed that, in both patients, the treated eyes became thousands of times more light-sensitive in low-light conditions, substantially correcting the original visual deficits. The researchers used, in all, nine complementary methods to measure the patients light sensitivity and functional vision. These included a test of room navigation skills in low-light conditions and a test of involuntary pupil responses to light. The tests consistently showed major improvements in rod-based, low-light vision, and the patients also noted functional improvements in their everyday lives, such as can [now] make out objects and people in the dark.

Just as striking was the rapidity of the improvement following therapy. Within eight days, both patients were already showing measurable efficacy, said study co-author Artur V. Cideciyan, PhD, a research professor of Ophthalmology at Penn.

To the researchers, the results confirm that GUCY2D gene therapy to restores rod-based photoreceptor functionsand suggest that GUCY2DLCA patients with more severe rod-based dysfunction are likely to benefit most dramatically from the therapy. The practical message is that there should be an emphasis on rod vision measurements at screening of LCA candidates and in monitoring them throughout a treatment trial.

The findings, the researchers said, also underscore the remarkable fact that in some patients with severe congenital vision loss, the retinal cell networks that mediate vision remain largely alive and intact, and need only the resupply of a missing protein to start working again, more or less immediately.

The ongoing clinical trial is registered at clinicaltrials.gov as trial NCT03920007.

Support for the research was provided by Atsena Therapeutics, Inc., the developer of the GUCY2D gene therapy; the National Institutes of Health (R01 EY11522); and by a CURE Formula grant from the Pennsylvania Department of Health.

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Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness - Newswise