ATL1102 US Patent - very interesting

https://www.freepatentsonline.com/y2020/0095587.html


Some interesting snippets:

The form of Muscular Dystrophy in a subject is selected from the group consisting of Duchene muscular dystrophy (DMD), limb girdle muscular dystrophy (LGMD), Becker muscular dystrophy (BMD), congenital muscular dystrophy (CMD including Fukuyama Type congenital MD and congenital MD with myosin deficiency), fascioscapulohumeral, oculopharyngeal, Emery-Dreifuss, and distal muscular dystrophy.

DMD, for example is often clinically diagnosed when infant motor milestones are delayed at 18 months. Early features of muscle weakness include a wide based gait, toe walking hyperlordosis of the spine, frequent falls, hypertrophy of muscles, such as the calf, deltoid, quadriceps, tongue masseters, difficulty getting up, arm weakness. Loss of ambulation typically occurs between 7 and 13 years of age in DMD, while later ambulation is characteristic of BMD. Cardiopulmonary deficits may also be apparent. Fatigue and speech development may also be delayed. However, no upper motor neurone signs or muscle fasciculation is observed.

Diagnosis of DMD may be confirmed by dystrophin immunofluorescence testing and/or immunoblot showing dystrophin deficiency, and a clinical picture consistent with typical DMD. Alternatively, gene deletions test positive (missing one or more exons) of the dystrophin gene, where reading frame can be predicted as ‘out-of-frame’, and a clinical picture consistent with typical DMD is indicative. In one embodiment, complete dystrophin gene sequencing may show a point mutation, duplication, or other mutation resulting in a stop codon mutation that can be definitely associated with DMD. A positive family history of DMD confirmed by one of the criteria listed above in a sibling or maternal uncle is also useful. Also used are assessments of DMD characteristic clinical symptoms or signs (e.g., proximal muscle weakness, Gowers' manoeuvre, elevated serum creatinine kinase level).

Suitable improved markers, signs and symptoms of MD or dystrophic myofibres/improved muscle function will be known to those of skill in the art. Suitable tests include those for increased motor, muscle, cardiac, blood flow, lung function over time during treatment.

In subjects with pre-clinical cardiomyopathy, cardiac efficacy based on serum biomarker response may be determined. This may be achieved by determining the levels of one or more markers such as myostatin ratio, cardiac troponins, cardiac BNP etc. eGFR changes may also be monitored. Other cardiac functions may be assessed by telemetry or rhythm abnormalities assessed by continuous mobile telemetry monitoring.

Further tests include testing for muscle oxygenation parameters and mitochondrial phenotype.

Reduced fibrosis may be assessed by MRI. Reduced muscle fat, reduced cardiac fibrosis, increased pinch strength, grip strength, improved cardiac and lung function tests. Other assessments look for a slowing in the rate of decline of the above functions.

Quality of life questionnaires are very useful in determining the effect of treatments.

Clinical outcomes may involve, for example, determining the percent change in normalized upper extremity reachable surface area, the percent change in cardiac circumferential strain by MRI, cardiac lateral and posterior wall strain is assessed.

Another useful test is to measure forced vital capacity, delayed loss of respiratory function, such as change in FVC 5p from baseline by spirometry measurements.

Motor function tests include determining the mean change in 4 standard stairs climb test before and after treatment, time to rise form floor, magnetic resonance spectroscopy mean change in fat fraction of vastus lateralis muscle at MRS, muscle testing of quadriceps, knee extensor peak torque measurement, ultrasound muscle microvascular blood supply to forearm.

Important clinical assessments include time to walk/run 6 or 10 meters, time to climb 4 stairs, time to descend 4 stairs, time to stand from supine position. Changes in weight, height, BMI may also be assessed.

Alternatively or in addition biomarkers from muscle biopsy assessments, pharmacodynamics markers measuring change in plasma biomarker panel measured by ELISA or proteomics, or change in circulating immune cell markers are assessed.

The EXAMPLES at the bottom of the patent application are also interesting.