A new option for Sanfilippo?

CLEVELAND—Aimed at discovering the potential of gene therapy intervention for rare genetic disorders, biopharma Abeona Therapeutics has revealed recent preclinical data supporting clinical trials for ABO-102—the AAV-based single intravenous gene therapy program for rare disorder, MPS IIIA, better known as Sanfilippo type A. The study, “Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery,” was published in the June issue of Molecular Therapy Methods & Clinical Development.

Sanfilippo is a rare autosomal recessive disease caused by genetic mutations that result in a deficiency of SGSH enzyme activity, leading to abnormal accumulation of glycosaminoglycan (specifically heparan sulfate, or HS) in the central nervous system and systemic tissues and organs. This accumulation of HS results in neurocognitive decline, speech loss, loss of mobility and premature death in children. One child in 70,000 births worldwide is diagnosed with Sanfilippo disease (of which there three other types in addition to type A), and there is no cure.

Although present at birth, Sanfilippo disease is not usually not diagnosed until the ages of four to six when the children have already begun regressing in speech and mobility and have begun to develop behavior problems.

The preclinical data supporting clinical trials for ABO-102 suggest there is potential for gene therapy intervention at intermediate stages of the disease, which is not specified. The benefits of gene therapy include improved learning ability, increased survival and improved GAG storage pathology in the CNS.

The study authors explained in their abstract that “We treated MPS IIIA mice at 1, 2, 3, 6 and 9 months of age with an intravenous injection of scAAV9-U1a-hSGSH vector, leading to restoration of SGSH activity and reduction of glycosaminoglycans (GAG) throughout the central nervous system (CNS) and somatic tissues at a dose of 5E12 vg/kg. Treatment up to 3 months age improved learning ability in the Morris water maze at 7.5 months, and lifespan was normalized. In mice treated at 6 months age, behavioral performance was impaired at 7.5 months, but did not decline further when retested at 12 months, and lifespan was increased, but not normalized. Treatment at 9 months did not increase life span, though the GAG storage pathology in the CNS was improved. The study suggests that there is potential for gene therapy intervention in MPS IIIA at intermediate stages of the disease.”

“The data support the clinical translation of ABO-102 for patients with Sanfilippo syndromes, and demonstrates AAV delivery to target tissues in the central nervous system, as well as peripheral organs, led to the underlying disease pathology,” Timothy J. Miller, Abeona’s president and CEO, stated in a news release. “This approach is also especially encouraging for potential treatment of patients with juvenile Batten disease, where patients are often initially diagnosed as a result of changes in vision, and the data demonstrate delivery of the AAV to the eye after an intravenous injection.”

Abeona Therapeutics previously announced that preliminary measures of clinically relevant biomarkers in the ABO-102 Phase 1/2 clinical trial provided promising signals of potential systemic and CNS clinical benefits for patients suffering with MPS IIIA.

“These promising data continue to reinforce our conviction that our novel portfolio of gene therapies including ABO-102 for MPS IIIA have transformational potential to treat devastating monogenic diseases,” commented Steven H. Rouhandeh, Abeona’s executive chairman.

“We’re excited about collaborating with our research partners and patient communities to expand ongoing clinical trials globally, as well as to leverage our insights to accelerate additional gene therapy candidates into clinical development,” he adds.

In gene therapy, DNA encodes a therapeutic protein is packaged within a “vector,” often a “naked” virus, which is used to transfer the DNA to the inside of cells within the body, according to Abeona. Gene therapy can be delivered by a direct injection, either intravenously or directly into a specific tissue in the body, where it is taken up by individual cells. Once inside cells, the correct DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patient’s disease and can provide long-term benefit. Delivered via a single injection, the drug is only given once.