From The Editor | February 28, 2023

Rare Disease Day 2023

Erin

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

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Today is Rare Disease Day, and the goal of Rare Disease Day is to improve knowledge among the general public of rare diseases while encouraging researchers and decision makers to address the needs of those living with rare diseases. In 2008 EURORDIS, with the Council of National Alliances, launched the first Rare Disease Day on February 29th, as it is a rare day that occurs only once every four years. It is otherwise celebrated on February 28th, as this month has a rare number of calendar days. Various advocacy groups, industry, academia, and the FDA dedicate time, research, community outreach, and educational sessions to spread data about rare diseases. Indeed, according to RareDiseaseDay.org, although Rare Disease Day is patient-led, everyone, including individuals, families, caregivers, healthcare professionals, researchers, clinicians, policy makers, industry representatives and the general public, can participate in raising awareness and taking action today for this vulnerable population who require immediate and urgent attention.

Manufacturing and Rare Diseases

I had the opportunity to contribute an article in Cell & Gene’s sister print publication, Life Science Leader magazine, for its annual Industry Outlook issue. You can read Part 1 and Part 2 here. The experts who participated in the interviews for that article provided so much detailed data, and I was unable to include everything in the article. Karen Kozarsky, Ph.D., Founder and CEO or SwanBio Therapeutics is one of the experts who participated in the article, and she provided sound information regarding advancements in gene therapy. The company’s initial focus is in the spinal cord-related disorders, beginning with adrenomyeloneuropathy (AMN), a form of x-linked adrenoleukodystrophy (ALD), which causes a disruption to the myelin sheath of the nerves. This occurs because of an inherited mutation of the ABCD1 gene. While SwanBio’s initial focus is on diseases that are both rare and serious, the broader vision is understanding the origin and treatment of disorders where therapeutic DNA has the potential to treat a range of neurological illnesses.

Here’s some of what we discussed that did not make it to print, and it is information that is critical in the on-going research for rare diseases. I asked her what went well in 2023 regarding gene therapies for the spinal cord. “It seems like every year in gene therapy is an exciting year with the incredible advancements that take place,” stated Kozarsky. “Having said that, it never feels like enough when it comes to progress. One thing that sticks out in my mind was the success of Novartis’ Zolgensma for spinal muscular atrophy. It is used as a one-time infusion into a vein. It provides a new copy of the gene that makes the human SMN protein. From what I’ve read, 2,300 babies have been treated so far worldwide. These babies are so severely affected, they don’t even sit up and most die between two and four years of age. Using this as a gene replacement therapy, the children are achieving milestones and living longer.

In terms of replication, although Novartis is developing the therapy, it was originally developed by a small startup much like Swan. They are demonstrating that innovations can come from a multitude of places and have impact. In terms of the science, this program helps de-risk other approaches like ours because they are using the same type of AAV we are using. The target tissue, spinal cord, is being reached paving the way for other iterative science. Many others can build on lessons they have learned.     

The other company getting a lot of attention is Taysha Gene Therapies, developing a gene therapy for giant axonal neuropathy (GAN) with the same target. Both therapies are well established in clinical trials for efficacy and safety and have orphan drug designation.”

Kozarsky went on to explain that as we iterate the science, we will reduce the need for how much we need to manufacture to study and eventually distribute gene therapies widely. However, companies are working independently and missing some commonalities we share with manufacturing challenges. One solution would be to pool resources and efforts. Why solve over and over when we could solve it only once? She stated that she sees progress all around her. For example, there are more physical facilities being built. Contract manufacturers building these sites could playing a key role in enabling many companies to overcome individual manufacturing capabilities. Let those who are expert in manufacturing take that piece and let the bench scientists work with them to enable better processes overall.

“Additional approaches come at the issue from the other direction: attempting to require less material for equally effective delivery,” says Kozarsky. “Those efforts center around finding improvements in delivery to be more specific for the target tissue. In addition, identification of new variations of the virus may make improve delivery to the appropriate tissues and cell types. The less you need to deliver, the lower the burden on manufacturing. It’s all about efficiency.”