Technical feasibility

SECTION I: Testing



Has the R & D result been tested?






The following question is replied according to the reply in question 1


If yes



In what mode has the result been tested?

•             Prototype

•             Pilot Application

•             Alpha/BETA testing






1b. Please describe and discuss the testing results


If no:



Describe what type of testing does the R&D result need?
The inventor discovered an allelic series of missense mutations in type IV collagen gene that induce mild to severe forms of muscle dystrophy in fruit fly Drosophila, affecting striated, smooth and cardiac musculature. Mammalian/human mutations perform muscular involvement also. The genetic tractability of the fruit fly allows testing under unlimited genetic backgrounds, a feature not available in mouse genetics. Therefore, fruit fly offers a high-throughput screening system for testing anti-dystrophic drugs.

Muscular dystrophy is a heterogeneous group of diseases genetically and clinically. Mammalian/human muscular dystrophy is characterized by progressive degeneration of muscle fibers, including proteolytic cleavage of structural proteins, myosins and actins, as common roots in all disorders. Three major proteolytic pathways are considered to be involved in dystrophic muscle wasting: Calpain, lysosomal and the ubiquitin-26S proteasome. Unfortunately, structural proteins of the muscle are not substrates of these proteolytic systems and an initiative proteolytic cleavage is considered to be involved in the initiation of muscle degradation.

A family of proteases was identified by virtue of their common recognition site for proteolytic cleavage on actin and myosin in fruit fly. We suppose that inhibitors of this protease family give the key in inhibiting progression of muscle dystrophy.


1d. What is the time needed for testing?
3 years.

Year 1

Hypomorph fruit fly mutants of these proteases are available commercially; homozygous mutants are viable and fertile, therefore these protease genes are not essential. In genetic crosses we produce double, type IV collagen plus protease mutants and test them for viability and fertility. Elevated survival and fertility are the signs to be followed. Once survival and fertility tests provide positive results, cellular and molecular markers will be established to show healing of dystrophy and preventing progression of the disorder.  These experiments allow selection of a single family member of these proteases and concentrate future work on it.


Year 2

Inhibitors of this protease family are available commercially. Enzymatic activity will be measured in vitro tests of genetically engineered, recombinant proteases to determine the level and mode of action. In parallel experiments we the project owner will test the efficacy of the inhibitors on survival, fertility, locomotion and flight in type IV collagen mutants. Behavioral tests will be followed by studying cellular and molecular markers. Usage of these inhibitors in humans will be searched in the pharmaceutical literature. “Humanized” inhibitors will be created by the producer of the inhibitors.

Year 3

“Humanized” inhibitors will be re-tested in our system to show their applicability in treatment of muscular dystrophy. Toxicity tests will be performed on laboratory animals. Phase one clinical studies involving healthy volunteers will go on.

1e. What is the cost needed for testing?
Year 1: 130 000 Euro

Year 2: 130 000 Euro

Year 3: 200 000 Euro




SECTION 2: Current Stage of Development



To what extent does the development team have technical resources for supporting the production of a new product? (Researchers, human resources, hardware, etc. )
The development team consists of three university professors, two postdocs, two predoctoral fellows and two PhD students. Two laboratory technicians will be hired.

All three professors have their own well-equipped laboratories where the project can be started immediately.

The development phase is based technically on classical and molecular genetics, biochemistry, cell biology and organic chemistry that are parts of the technical repertoire of the participating laboratories.


What are the technical issues that need to be tackled for full deployment, if needed?
There are no technical issues to be tackled for full deployment during ant-dystrophic drug development.




What additional technical resources are needed for the production of this new product?
Additional technical resources include instrumentation for fruit fly cell culturing, transfection and recombinant protein purification.

In the third year phase I clinical studies can be started.




Overall assessment of the current stage of technical development.
Genetic diseases, including muscular dystrophies are rarely curable directly. Gene therapies are still in their infancy and its clinical application is very limited.

Therapy of muscular dystrophies relies on classical treatment, assistive devices that can improve quality and sometimes length of life of patients with muscular dystrophy.

Muscular dystrophy can restrict the flexibility and mobility of joints. Limbs often draw inward and become fixed in that position. One goal of physical therapy is to provide regular range-of-motion exercises to keep joints as flexible as possible.

Braces can provide support for weakened and progressively wasting muscles and help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Other devices — such as canes, walkers and wheelchairs — can help maintain mobility and independence. Respiratory muscles involvement needs to apply a sleep apnea device may help improve oxygen delivery during the night. Some people with severe muscular dystrophy may need to rely on a ventilator.

Surgical remedies are an option for several of the problems common to muscular dystrophy. Tendon surgery can loosen joints drawn inward by contractures and to correct a sideways curvature of the spine that can make breathing more difficult.

All above treatments burden the health care systems worldwide; a radical new product definitely will reduce the costs of caretaking and treatment.

This proposal of the inventor, however, is based on eradicating of the initial step of muscle dystrophy by inhibition of the proteolytic cleavage of bulk muscle proteins actin and myosin, which in turn provides substrates for the main proteolytic pathways, calpain, lysosomal and the ubiquitin-26S proteasome.

SECTION 3: Deployment


Define the demands for large scale production in terms of
  • Materials
En gross synthesis of anti dystrophic drug at pharmacologic level; requirements of pharmaceutical industry.
  • technologies, tools, machineries
Pharmaceutical-level product plant, depending on market demands


  • Staff effort
Normal industrial organization at the level of mass production:


Quality control

Quality assurance





SECTION 4: Overall Assessment



What is you overall assessment of the technical feasibility of the research result?
The three years developmental phase will lead to the discovery of drugs which prevent progression of muscular dystrophy. The idea of this proposal, to our knowledge is new, similar results are not available in the muscular dystrophy literature. The key point of the proposal is to discover non-toxic protease inhibitors, possibly with a future oral application. Enzyme inhibition by natural substrate analogs is a traditional way applied in pharmaceutical industry. Enzyme kinetic studies have a tradition of several decades, even a century.

The project owner regards that one version of the invention could be distributed as nutraceutical supplement, the licensing and approval procedure could be finished in the third year and the experimental production can be started.

Technically the project is feasible.






Please put X as appropriate. 1 2 3 4 5
Adequacy of testing activity undertaken so far     X    
Adequacy and availability of technical resources of the development team         X
Current development stage     X    
Overall technical feasibility         X


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