In a press release from late May 2021, AAV gene therapy company and Bayer AG subsidiary Asklepios BioPharmaceutical, Inc. (“AskBio”) shared that the FDA approved its Investigational New Drug (IND) application for LION-101. This gene therapy, delivered via rAAV vectors, is designed for patients with limb-girdle muscular dystrophy (LGMD). In particular, LION-101 was developed to treat patients with LGMD type 2I/R9. Now that the IND has been cleared, AskBio is able to begin a Phase 1/2 clinical trial to evaluate this gene therapy.

LION-101

According to AskBio’s The AAVengers newsletter, LION-101 is designed to assist patients with damaged or nonfunctional FKRP genes:

We provide a correct copy of the FKRP gene using the shell of a harmless virus that has had the viral DNA removed. The gene is delivered to the voluntary and heart muscles, where it is expected to begin working like a non-damaged FKRP gene.

Earlier, AskBio submitted an IND. Ultimately, the IND asks the FDA for permission and authorization to administer an investigational treatment to humans. Because the FDA cleared the IND, AskBio is now able to proceed to clinical trials. Specifically, AskBio will evaluate one intravenously administered LION-101 dose in pediatric and adult patients with LGMD2I/R9. The trial should take place by the first half of 2022.

In preclinical studies, LION-101 was safe, efficacious, and well-tolerated. Thus, researchers are excited to see whether LION-101 also benefits patients within a clinical setting.

Limb-Girdle Muscular Dystrophy (LGMD)

There are multiple genetic mutations associated with LGMD, disorders under the larger umbrella of muscular dystrophy. For example, LGMD2I/R9, as described above, results from FKRP gene mutations. Regardless of the specific mutation, LGMD causes progressive muscle weakness, wasting, and loss of muscle mass in proximal muscles. Proximal muscles are muscles close to the body. Thus, patients with LGMD typically have shoulder, arm, pelvis, and thigh muscles impacted. As the condition progresses, some patients may use mobility assistance (such as wheelchairs). Symptoms include:

• Developmental and intellectual delays
• Scoliosis (abnormal spinal curvature)
• “Waddling” gait
• Difficulty walking, running, or climbing stairs
• Calf muscle overgrowth
• Difficulty reaching, holding arms out, or carrying heavy objects
• Shoulder blades which stick out from the back
• Cardiomyopathy (weakened heart muscle)
• Muscle contractures
• Joint stiffness
• Difficulty breathing
• Slurred speech

In patients with limb-girdle muscular dystrophy type 2I, symptoms typically appear in adolescence. Within 20-25 years following diagnosis, many patients require mobility assistance. In particular, LGMD2I is inherited in an autosomal recessive pattern. This means patients must inherit one defective gene from each parent. Outside of the symptoms listed above, additional symptoms for LGMD2I include:

• Elevated serum creatine levels
• Decreased muscle tone
• Frequent falls
• Hunched back