Abeona Therapeutics Uses Next-Generation AAV-Based Gene Therapy


Adeno-Associated Virus (AAV) vectors are currently among the most frequently used viral vectors for gene therapy. At recent meetings of the American Society for Gene Therapy, nearly half of the presentations involved the use of AAV. In fact, Pfizer recently snapped up a gene therapy start-up Bamboo for $150 million that also utilizes the AAV delivery tool.

Not surprising, the current wave of clinical applications of gene therapy is largely based on a new family of AAV vectors – the most commonly used viral vectors today. AAVs are used to ferry corrected genes and other small nucleic acids into cells. Translation of AAV gene therapy into the clinic has largely been in the treatment of disabling and lethal rare genetic diseases where the need is the greatest.

One biotech working in this area is Abeona Therapeutics, which is using the next- generation AAV-based gene therapy for MPS III (Sanfilippo syndrome) and is hoping to address Sanfilippo Syndrome involving the use of one-time delivery of a normal copy of the defective gene to cells of the central nervous system with the aim of reversing the effects of the genetic errors that cause the disease.

The first two patients who were treated this spring under the auspice of Kevin M. Flanigan, MD, Principal Investigator with the Center for Gene Therapy at Nationwide Children’s Hospital, are both showing favorable responses so far. The company recently reported seeing favorable early results, including detecting biopotency signals in their first two patients.

Children with the disease are unable to appropriately break down sugar, thus causing carbohydrates to accumulate throughout the somatic and central nervous system.
Although children with the disease appear normal at birth, they later show severely delayed neurological development and become unable to talk, walk, or even feed themselves. Sanfilippo syndromes are a group of four inherited genetic diseases, each caused by a single gene defect described as type A, B, C, or D, is a lysosomal storage disease, a group of rare inborn errors of metabolism resulting from deficiency in normal lysosomal function.

The incidence of MPS III (all four types combined) is estimated to be 1 in 70,000 births. Mucopolysaccharides are long chains of sugar molecule used in the building of connective tissues in the body. There is a continuous process in the body of replacing used materials and breaking them down for disposal.

In MPS III, the predominant symptoms occur due to accumulation within the central nervous system, including the brain and spinal cord, resulting in cognitive decline, motor dysfunction, and eventual death. Importantly, there is no cure for MPS III, and treatments are largely supportive care.

After a single dose in Sanfilippo preclinical models, ABO-101 induced cells in the central nervous system and peripheral organs to produce the missing enzymes and help repair damage caused to the cells. Preclinical in vivo efficacy studies in Sanfilippo syndrome have demonstrated functional benefits that remain for months after treatment. A single dose of ABO-101 significantly restored normal cell and organ function, corrected cognitive defects that remained months after drug administration, increased neuromuscular control, and increased the lifespan of animals with MPS III over 100% 1 year after treatment compared to untreated control animals. These results are consistent with studies from several laboratories, suggesting AAV treatment could potentially benefit patients with for Sanfilippo syndrome Type A and B, respectively. In addition, safety studies conducted in animal models of Sanfilippo syndromes have demonstrated that delivery of AB0-101 are well tolerated with minimal side effects.

Abeona Therapeutics Inc. is also developing ABO-201 (AAV-CLN3) gene therapy for juvenile Batten disease (JBD); and ABO-301 (AAV-FANCC) for Fanconi anemia (FA) disorder using a novel CRISPR/Cas9-based gene-editing approach to a gene therapy program for rare blood diseases.