Fatal and debilitating, DMD is a rare childhood genetic disease confining boys into wheelchairs by age 12 and often suffocating them by age 20. The genetic defect manifests in the absence of a membrane structural protein called dystrophin, without which, the muscle fibers break and die as the bones elongate beginning at age 5. The anti-gravitational muscles usually lose 50% of muscle fibers and strength by age 9 and 80% by age 12. Muscle fiber degeneration also strikes the neck, the back, the girdles and the upper limbs, deforming and weakening the children to the point that they cannot breathe. A logical treatment to replenish the dead muscle fibers with live ones and genetically repair the degenerating ones is called Myoblast Transfer Therapy (MTT).

Genetically normal myoblasts are obtained in tens of billions from the primary culture of satellite cells isolated from muscle biopsy of pathogen-free healthy male donor. Myoblasts are differentiated cells destined to become muscles. Mammalian evolution over 160 million years witnesses their unique ability to fuse during muscle development and regeneration. Implanted myoblasts naturally fuse among themselves to form genetically normal muscle fibers to replenish dead fibers. They also fuse with dystrophic muscle fibers, inserting their nuclei that carry the normal genome to produce genetic complementation repair. As such, MTT is a somatic cell therapy and a gene therapy, or more correctly, a genome therapy with nuclei transfer.

First published in Lancet on July 14, 1990, MTT is the world’s first human gene therapy to have replenished dystrophin, a structural protein not produced in DMD muscles [1] . That was the dawn of Regenerative Medicine in the field of somatic cell therapy. If replenishing dystrophin is all that it takes to cure DMD and to be granted FDA Biologic License Approval (BLA), my team had achieved that in the year 1990, if not, then in the years ensuing. We even demonstrated that dystrophin persisted in the same muscle at six years after MTT [2] . The work came after 15 years of basic research supported by 11 years of top-priority NIH (National Institutes of Health) grants.

The organization that I founded, Cell Therapy Research Foundation (CTRF), had requested granting of a Treatment IND (Investigational New Drug) in 1998, but it was turned down. FDA admitted that functional data had demonstrated efficacy, but had question about histology. It is not difficult to see histologic efficacy in our publications dated before November 1998 [1] - [11] . In reality, functional improvement in muscle contraction should be the primary end point for these clinical trials and not dystrophin production alone.

I pioneered and developed MTT to treat DMD, unto fast-track Phase III clinical trials with approval to charge for 5 consecutive years following progress reviews by the Center for Biologics Evaluation and Research (CBER). At the height of my career, patients from 20 countries came to USA to seek treatment in the non-profit CTRF that I founded and chaired. For political and financial reasons that were not obvious at the time, my research was abruptly put on hold by the FDA and I was forced to abandon my mission. By disqualifying me as an investigator the FDA forced me out of the USA where I spent 29 years of my academic career beginning as an Assistant Professor then Full Professor and Chairman of the non-profit CTRF. I had no alternative but to leave the USA in order to continue with my mission in life, knowing full well that no one else in the world came close to my knowledge on the technology.

The following video segment showcases the physical improvement of dystrophy patients after MTT as documented by representative patients (24 cases), parents and news media:

http://www.youtube.com/watch?v=mU3-_IQ15x4 (English)

https://v.qq.com/x/page/n0522dwcoi5.html (Chinese)

The benefits versus risks ratio of MTT is outstanding. Many of the DMD boys treated only once by my team 20 years ago are currently alive in their 30’s and 40’s. Unfortunately, within these decades, millions of DMD patients lost the opportunity to be treated by MTT due to the actions or inactions of the FDA.

The benefits of MTT can only be obtained with 50 billion myoblasts implanted into 82 muscle groups of each DMD boy. My team is the only one in the world which is capable of producing such effects using the innovative techniques that we invented and developed over the years [3] [4] .

FDA began regulating cell therapies in the year 1993. From 1994 to 1999, FDA allowed CTRF to charge upon satisfactory annual review of the progress of the Phase II and Phase III clinical trials on DMD, Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD). By November 1998, the BB-IND 5108 trials were allowed multicenter Phase III Fast Track development. The Public Health Ministry of the Russian Federation, the Hungarian National Insurance Fund Administration, the German Health Insurance system, and the Brazilian government were paying CTRF in Memphis, Tennessee US$150,000- for a MTT for each of their DMD citizens. To meet American demand, many foreign patients had to be turned away because of the limited number of subjects allowed by the FDA in the studies.

My team continued to publish quality controls of myoblast manufacture, including cell identity, purity, quantity, viability, potency, sterility, mycoplasma and endotoxins in dose-escalation, natural history and randomized, double- blind studies. Much of what my team published found their way into the April 1, 1997 revision of the FDA Code of Federal Regulation (CFR) 21.

Instead of granting BLA to BB-IND 5108, “Cultured Allogeneic Myoblasts, and Cyclosporin (Sandoz)”, FDA initiated a guided investigation of CTRF in 1999, stopped all its clinical trials, physically destroyed its storage of myoblasts without testing, and capriciously initiated disqualifying me as an investigator. The destroyed myoblasts represented years of painstaking R&D and financial investment. They belonged to the same batches of cells that kept patients alive as of today.

In the lengthy, make-believe “483”s that described logistic rather than scientific deficiencies, there was not a statement describing death or permanent severe adverse reaction of any trial subject. There was no statement describing dishonesty or forgery. Our response to the “483”s were simply ignored. CTRF went bankrupt after FDA would not allow the study to move forward.

In 2016, US FDA approved Exondys 51 developed by Sarepta Therapeutics as the first DMD drug. They approved Exondys 51 on fast track, priority review, and orphan drug designation. Accelerated approval made this drug available to patients based on initial data. The aftermath was not pleasant.

The FDA News Release on September 19, 2016 documented that, “A clinical benefit of Exondys 51, including improved motor function, has not been established” and that, “The most common side effects reported by participants taking Exondys 51 in the clinical trials were balance disorder and vomiting” (Attachment 1) [12] . The Associated Press on the same day called Exondys 51 “the largely unproven medication.” [13]

In the following months, media outlets and reputable individuals lambasted the FDA’s egregious decision making [14] [15] [16] [17] [18] . This controversy was not only evident in the public eye, but also internally within the FDA itself [19] [20] [21] . Prior to his retirement, John Jenkins, the Director of Office of New Drugs (OND), presented the lessons learned from the Exondys 51 catastrophe at a NORD summit meeting. Furthermore, the FDA’s refusal to disclose records sparked a federal lawsuit from a top American science journalist and New York University professor, Charles Seife [22] [23] .

It is clear the FDA exercised a different standard when approving Exondys 51, but did their actions stem from incompetence or corruption? Further yet, could a contrary situation have occurred where a viable treatment option was not only declined, but maliciously destroyed? Could these dishonest and unlawful practices date back to nearly two decades ago? Why was MTT in BB-IND 5108 subjected to a hostile and unprecedented standard towards the end? Tables 1-3