Monogenic diseases arise from inherited genetic mutations. They can be severe, life-long, and lethal. Many also have no treatment options. Gene and cell therapies offer a new avenue of treatment and over the past decade there has been monumental success in using gene therapy to treat highly debilitating genetic diseases, including the hemophilias, immunodeficiencies (ADA-SCID, X-SCID, WAS), lysosomal storage disorders (MLD, ALD), sickle cell anemia, and spinal muscular atrophy. This is just the beginning.
In synergy with Mount Sinai’s clinical genetic efforts, scientists and physician scientists in the Icahn Genomics Institute (IGI) are working to develop novel gene therapies to treat genetic disease. Our clinical genetics group, led by Manisha Balwani, MD, MS, ran Phase I/II and Phase III clinical trials of givosiran, a short interfering RNA (siRNA) drug that works by RNA interference (RNAi). They demonstrated that givosiran can successfully treat the debilitating genetic diseases called acute hepatic porphyrias, leading to the second FDA-approved RNAi drug. The concept for this drug began at Mount Sinai with work in preclinical models showing that RNAi could be an effective treatment for the porphyrias, representing a bench-to-bedside success.
New gene therapies are also being developed at the IGI to treat more complex diseases, including cardiac disease, immunodeficiencies, and epilepsy, using a variety of modalities such as AAV gene delivery, CRISPR gene editing, and antisense oligonucleotides.