Shahriar's Story
Petitioner Shahriar (“Shah”) Minokadeh is a physician who has been battling ALS since 2011. Medicine is in his family’s blood. He is the son of an anesthesiologist and one of three sons who all pursued a career in medicine. Shah was accepted into an accelerated medical studies program where he finished a bachelor's degree and medical school at the age of 24. He trained in anesthesiology at Johns Hopkins and went on to sub-specialize in pain management at UC San Diego. He was in the prime of his life when he received the devastating diagnosis of ALS at just 35 years old.
Like fellow Petitioners Mayuri Saxena and Kade Simons, Dr. Minokadeh is a carrier of a Variant of Uncertain Significance of the SETX gene: c.907 T>A (p.Ala969Ala). Shah’s SETX variant is not on ClinVar.
Dr. Minokadeh’s first symptoms were mostly upper motor neuron dominant and he experienced weakness when running. But his ALS was slow progressing so he continued to practice medicine until December 2015. Four years after symptom onset, he was forced to retire when he could no longer walk and his hands had become weak. However, he had no bulbar symptoms; he was still speaking and eating normally and had movement in his arms.
For many reasons, Dr. Minokadeh brings a unique perspective to Petitioners’ case. First, as a patient, he participated in the NP001 trial that showed efficacy with some people stabilizing or regaining bulbar and respiratory function. But then couldn’t get more of that or any other investigational drugs. Second, as an anesthesiologist, he has done thousands of lumbar punctures in his practice, the method of delivering NurOwn. Third, as a patient advocate, he has a historical perspective of fourteen years of communications with the FDA; and finally, as he went from a thriving clinical practice to a man who is now trached, he has witnessed the myriad of legislative wins and regulatory failures. Despite this historical knowledge and his quite relevant medical practice, Dr. Shahriar Minokadeh was not chosen to speak at the AdComm’s Open Public Hearing. He and both his physician brothers did submit Public Comments: Shahriar, Anush and Ardalan Minokadeh.
Dr. Minokadeh was fortunate to participate in a Phase 2A clinical trial of a small molecule drug called NP001 by drug sponsor Neuraltus. Even though he was on the lower dose, he believes that small molecule drug helped slow his progression. Five years later, in June 2016, he emailed Dr. Woodcock and shared his perspective.
“I'm writing to you as both a physician and as a patient who is suffering from the dreadful disease of ALS. I am urging you to please show your compassion and understanding for people with terminal illnesses by helping expand access to experimental drugs.... By the time a current experimental medication gets through research and FDA approval, nearly all of us alive with ALS today will be gone. I participated in a trial in 2011 using a drug called NP001. It's slowed my progression and multiple others have said the same. Due to a lack of funding, they have not proceeded with the next trial. Due to the strict regulations, they have begun to offer this medication to patients in Europe. I feel it's a travesty that US patients -- facing a terrible quality of life, followed shortly after by certain death -- are not given the opportunity to access these drugs. Please expand Right To Try laws and any measures that speed up access to investigational medications for people with terminal illnesses.”
Eventually the company that made NP001 went out of business and the assets were purchased by Neuvivo who now has a pending NDA for a drug that worked on Shah and many others 14 years ago.
Although grateful to be a trial participant, Dr. Minokadeh has criticized the FDA’s inhumane regulatory requirement for double-blind protocols in ALS trials that leave as many as 50% of dying patients on placebo without actual treatment during the trial; and then without an open label extension, they have no hope after the trial. This is unimaginable in a 100% fatal disease with rapid progression to paralysis.
But Dr. Minokadeh’s lack of access to investigational drugs didn’t stop with that NP001 trial:
“I’ve been locked out of any clinical trials or access to investigational treatments since 2013 because of trial restrictions. My family, friends and I have corresponded with the FDA, pharmaceutical companies and neurologists countless times. Despite my own medical background, knowledge, and connections in medicine, I've not been able to access a single investigational therapy for seven [now eleven years]. The existing pathways of right to try, compassionate use or expanded access, to this day, have only been empty words ... I and many other ALS patients heard these words repeatedly, and unfortunately most died while they fought.”
Dr. Minokadeh again wrote to the FDA:
“I have been in contact with numerous other patients and neurologists throughout the years and have extensively researched and tried off-label treatments. I have never seen the results we are seeing and hearing with the Phase 3 trial of Brainstorm (Nurown). For the first time we have reputable people with unprecedented levels of improvement (most recently Matt Bellina from Right To Try).
I live every day suffering and facing the possibility of dying. I know all diseases have heterogeneity and everyone may not have the same response, but this is the case even with chemotherapeutic agents in cancer treatments. I strongly believe you all have the authority and moral obligation to allow expedited access of NurOwn....”
In 2015 when Shah was forced to leave his medical practice, it occurred concurrently when people in the Phase 2 NurOwn trial were reporting improvements in function. Shah became good friends with Bobby Forster, one of the NurOwn participants who had a profound response and regained function in Phase 2. Shah has been aggressively fighting for the FDA’s regulatory flexibility since that time. All to no avail.
Shah tried repeatedly to get access to NurOwn both via Right to Try here in the US and via the Hospital Exemption program in Israel. But even with the law and several medical professionals in his corner, Shah succeeded. Brainstorm responded to the request of Dr. Minokadeh and his physician brothers:
“Investigational therapeutics, such as NurOwn® are highly regulated by the US FDA, and all patients must meet the investigational protocols... If the patient you have referenced does not meet the clinical trial eligibility, he cannot participate in the trial as all participants must meet all inclusion and exclusion criteria. Due to privacy and regulatory issues the Company cannot comment on a patient’s eligibility. That is a conversation for the patient and his clinical team to discuss. Additionally, we would direct you to the Company’s publicly stated policy on Right To Try. In a perfect world, small biopharma companies like BrainStorm would have the limitless capacity and resources to give every patient access to experimental treatments, as well as the assurance of knowing that these treatments are safe and effective for every patient seeking them. But regrettably, the practical reality is resources are limited, experimental treatments must be tested for safety and efficacy, and the path to approval of a new treatment is lengthy. With the greatest sympathy for the many thousands of ALS patients seeking access to experimental treatments, BrainStorm cannot offer pre-approval access to NurOwn. Thank you for recognizing that we are bound by many federal healthcare laws and regulations including patient confidentiality. Brainstorm stays fully committed to advancing the Company’s pivotal phase 3 ALS trial towards a BLA submission. If the outcome of the trial is successful, we hope to be able to bring a much-needed solution to ALS patients as quickly as possible.”
That was six years ago. In 2019, Dr. Minokadeh was using NIV to breathe and had lost most motor function in his legs. But he was still able to speak some words. In 2022, he underwent a tracheostomy. Today his only way to communicate is with his eye gaze. Six years ago, Dr. Minokadeh told Spectrum News:
“People like me feel like time is running out with no options, with no treatments that we can try to save our lives.”
Indeed, when he couldn’t get access to NurOwn, Shah tried some of the most aggressive options. In 2016, he had an Ommaya reservoir placed in his skull. Shah used the catheter to try delivering adipose-derived mesenchymal stem cells directly to his CSF to see if he could mimic what NurOwn was doing for people who were in the trials. He did this for approximately 6 months and had absolutely no response. In his “n of 1” study, Shah proved to himself that the mesenchymal stem cells aren’t what causes the disease-modifying response with NurOwn; rather, he concluded that it's the neurotrophic factors that the stem cells deliver all throughout the CNS.