Boston’s Cure Rare Disease on the Cusp of CRISPR-based Personalized Treatment for type of Duchenne Muscular Dystrophy

Mar 9, 2020 | CRISPR/Cas9, Cure Rare Disease, DMD, Duchenne Muscular Dystrophy, Gene Editing, Gene Therapy

Boston’s Cure Rare Disease on the Cusp of CRISPR-based Personalized Treatment for type of Duchenne Muscular Dystrophy

In a compelling story of brotherly love, familial connection, and the power of entrepreneurial energies, a 28-year old Boston-based entrepreneur, whose brother has Duchene Muscular Dystrophy, launched a biotech nonprofit organization to cure his brother using a novel, personalized, gene-based therapy. He gained the attention of a prominent research scientist in the region, and they now are pursuing a target. A recent Harvard graduate, Rich Horgan, is an inspirational young man.

Duchenne muscular dystrophy (DMD)

DMD is a severe type of muscular dystrophy involving muscle weakness—it usually starts around the age of four in boys and rapidly deteriorates from there. Typically, muscle loss occurs first in the thighs and pelvis, followed by the arms. Thereafter, those afflicted have a hard time even standing. Most patients cannot walk by age 12. The disorder is X-linked recessive. About two-thirds of cases are inherited from a person’s mother, while one-third of cases are due to a new mutation. It is caused by a mutation in the gene for the protein dystrophin—important for the maintenance of the muscle fiber’s cell membrane. There is no known cure and affects about one in 5,000 males at birth.

The New Organization: Cure Rare Disease

The organization Rich Horgan founded to find a cure for his brother Terry, Cure Rare Disease, is not even two years old and is already extremely busy. Based in Boston, MA, the organization’s first target is a customized gene therapy treatment for Terry’s combat against Duchene muscular dystrophy (DMD). By January 2020, three other patients were in line as well. According to a report in January 2020, the organization was “on the cusp of a major breakthrough”, according to the recent Harvard Business School graduate.

The organization has secured over $1 million and benefited from the backing of global philanthropist and billionaire Len Blavatnik. Now collaborating with 15 researchers at seven institutions, they are also contributing to FDA policy on individualized medicine in addition to an insurance reimbursement—not to mention a database accumulating data about mice on different Duchenne mutations.

Local Scientific Talent & CRISP/Cas9

It doesn’t hurt that Rich Horgan happens to reside in Boston, perhaps the most prominent biotechnology cluster in the world. Horgan ’s drive and the mission-based cause have gained the attention of very prominent researchers and scientists. For example, prominent Charles River Laboratory research scientist Lauren Black joined the cause. According to the recent news in the Boston Herald, Black “jumped” at the chance to make a difference stating, “When you know you have something that someone needs badly, it’s an immediate yes.” To contribute to the cause, Black commenced with the development of rat models with DMD to supply the investigators to test experimental drugs on the rats, as the cause of DMD is a defective gene—the answer for such a drug associated with gene therapy.

Hence the nonprofit, by partnering with Charles River Labs and the Black relationship, Cure Rare Disease was able to implement groundbreaking methodology with precision medicine by developing customized therapeutics designed using CRISPR gene-editing technology.

A brilliant entrepreneurial networker and organizer, and through his Harvard and Boston-based academic contacts, Horgan connected with others such as Timothy Yu, a Boston Children’s Hospital neurologist and one of the earliest adopters of “customized medicine” for Batten disease, a rare inherited ailment. Dr. Yu became a key advisor for Cure Rare Disease, contributing to the personalized model that could ultimately help Rich’s brother Terry. 

Horgan has met and secured support from other prominent contributors from Stanley Nelson (UCLA) to Monkol Lek, Ph.D. (Yale School of Medicine). 

Harvard Education Pays Off

Summarizing his powerful Harvard education, Horgan noted: “Harvard taught me that while you may not be able to do the science, you can enable people to come together.” He added, “You can paint the vision. You can bring this collective group together and orient them in a direction that is going to generate and create positive success.” Of course, this young man has more than a Harvard education. The love of his brother and the quest for his brother’s cure lit a fire of passion that has driven exceptional—actually, beyond exceptional—results. A gifted individual at a young age, Horgan has conceived, launched, and now operates a very important organization.

More on the Technology

As reported by Hawken Miller in Muscular Dystrophy News Today, the Cure Rare Disease team employed gene-editing technology, inserting CRISPR activation into the harmless adeno-associated virus (AAV) delivery system. They will test this approach in mice bred with the mutated human version of DMD—that altered gene in DMD patients such as Rich’s brother Terry. If all goes well, the nonprofit will seek approval to treat Terry with the gene therapy. This, according to at least one report, would be one of the first, if not the very first, in vivo CRISPR activation performed in the United States.

Other Approaches to DMD

Sarepta Therapeutics has two FDA approved “exon-skipping therapies” known as Exondys 51 (eteplirsen) and Vyondys 53 (goloirsen) for Duchenne patients with mutations in specific exons. These are the tiny bits of DNA that contain information to produce proteins, reports Muscular Dystrophy News Today. In the case of DMD, dystrophin is the protein that is needed for the muscles to function properly. Developed for the nearly 13% of patients carrying mutations in exon 51 of DMD, Exondys51 is now available while Vyondys 53 is for those with gene alterations in exon 53. However, these therapies would not work for Terry Horgan as his disease-causing alternation is in exon 1—hence, he is a candidate for personalized therapy.

Moving Forward

Horgan reports that his organization is planning on an application for the world’s first human administration of gene therapy for this form of DMD by late 2020, pending FDA approval. Horgan acknowledges to the Boston Herald that moving forward is also scary—“to be the first one because the knowledge about the drug is limited.” Rich Horgan , if Cure Rare Disease can get to the finish line with a drug approval and administer a successful personalized gene therapy for brother Terry, literally is helping to make history.

Call to Action: Interested in contributing to the cause of personalized gene therapy treatments for rare diseases such as DMD? Visit Cure Rare Disease.

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