How this Indian-origin mother is trying to spotlight a rare skeletal disease

Neena Nizar grapples daily with the challenges of living with Jansen's Metaphyseal Chondrodysplasia, an exceedingly rare and formidable skeletal disease

Neena Nizar is a remarkable individual who leaves a lasting impression on anyone she meets. Despite her petite stature, her presence commands attention, captivating everyone in the room. However, behind her electric personality lies an extraordinary story of courage and determination as she grapples daily with the challenges of living with Jansen's Metaphyseal Chondrodysplasia—or Jansen’s—an exceedingly rare and formidable skeletal disease. In addition to her own struggles, US-based Nizar shoulders the weight of caring for her two sons, Arshaan and Jahaan (now 15 and 13 respectively), who face similar struggles as they grow older.

Jansen's, an extremely rare genetic disorder affecting only a few dozen individuals worldwide, presents a daunting reality for those diagnosed with it. With no cure in sight and the uncertainty surrounding its progression and long-term impact, patients like Nizar and #TheAdamBoys (a hashtag that was created to draw attention to the determination her sons epitomise) endure daily challenges, dealing not only with physical struggles but also the associated fear and emotional burdens.

Over the years, Nizar has transformed her turbulent experiences with Jansen’s into a lifelong commitment. Her determination and passion have driven her to traverse countries, from India and the US to the United Arab Emirates, eventually settling in the US, in pursuit of researching Jansen's and advocating for individuals with rare diseases. Through her charity, The Jansen’s Foundation, Nizar’s unwavering dedication has earned her the status of a trailblazer, as she works tirelessly to develop ground-breaking initiatives with the potential to transform lives.

In a freewheeling chat, Nizar graciously shares her extraordinary journey, offering insights into her powerful advocacy for change in the complex world of big pharma and research on rare disease. 

For those reading about you for the first time, can you share with us your personal journey with Jansen’s and how it motivated you to start The Jansen's Foundation?

In 2008, my husband Adam and I faced uncertainty and fear while planning to start a family due to my pre-existing skeletal condition. “You will never have a child; if you do, your legs will break out from under you; the child will not make it to term.” I painfully recalled these forewarnings as strong contenders for never wanting to marry, let alone carry a child. Then, Adam said, “You have to give love a chance. Anything is possible if God wills it.” True enough, on 3rd  July 2008, I delivered a beautiful baby boy. We named him  ‘Arshaan,’ Persian for ‘A Good Man’.

For the next two years, we basked in watching our boy achieve all his milestones. Talking at nine months, walking at a year. It was clear Arshaan had taken after me with his big expressive eyes, but there was no sign of my, or any other disease in his body. However, when he turned two, worrying symptoms began to appear. By May 2010, we were preparing to welcome a second baby into our lives. But the ultrasound during the fourth month revealed “limbs about 6 weeks off”. Suggestions were made to terminate the pregnancy. However, we stood firm in our faith; we were going to love our baby, no matter what. On 14th October, 2010, I gave birth to Jahan, Persian for ‘Savior’.

Help us visualise the experiences and challenges of those early years and how you discovered that the three of you had Jansen’s.

By age two, Arshaan was walking with a distinct waddle. There was marked swelling in his knees, and his once long pointy fingers now looked choppy and weak. I started digging up my old medical records to see if there was something that could lead us in the right direction. However, the deeper I dug, the more I was convinced we were dealing with something so confounding and mysterious it would take a miracle to find the truth.

Every ultrasound of our younger son, too, filled us with worry. I knew if we stayed put in Dubai with no answers, I would lose my mind. I decided to quit my job as a teacher and travel back home to India. The next seven months were a blur. In sheer blindness, we groped at endless hours with experts the world over. The reply was always the same: “We don’t know what’s going on with your boys.” After endless dead ends, I was ready to give up. But we made one last attempt.

After a seven-hour journey, we met Dr. Sheela Nampoothiri, a pediatric geneticist in Kochi. With a calm demeanor, she confidently diagnosed Jansen's Metaphyseal Chondrodysplasia, an extremely rare skeletal condition affecting only 30 cases worldwide [then]. After 32 years of living with misdiagnoses of "rickets," "vitamin D deficiency " and an overwhelming "I don't knows”, we were able to name the enemy.

What factors influenced your choice to move to the United States of America?

Just one, actually, when I Googled the word ‘Jansen’s’ that November night in Kochi, I only found a single paper online written by Dr. Haralad Jueppener, titled Jansen's and the potential of an inverse agonist to turn off the overactive PTH receptor. We then decided to return to America and seek Dr. Jueppener's expertise for a better life for our boys. At the time he was our only hope!

In March 2015 the boys underwent surgeries in the US to fix their leg deformities. While the initial results were promising, the improvements were short-lived as new bone formations brought back the bends. We knew we had to find a permanent cure for this relentless condition. In February 2016, we finally met Dr. Juppener in person. The researcher, whose lab had been responsible for mapping the H223r mutation that causes Jansen’s, had been researching the disease for 20 years, but had never met a patient with the condition. Then he met me and my boys. The meeting was monumental for both doctor and patients. We were excited to learn of all the wonderful work Dr. Jueppner and his team had been doing and were totally taken aback to learn about the Jansen’s mice he had in his Boston lab! Now we could directly help with his research by providing valuable data via blood tests and lab work. In November that year, we travelled to UCLA to give sample bone and cells to better understand the condition.

Most of us cannot even imagine what living with a rare disease is like—could you help us understand?

Amidst the physical hardship, the emotional toll is equally staggering. The constant search for specialised care and understanding can leave one feeling lost and disheartened. Simply getting to a diagnosis of a rare disease can be a complicated, lengthy, and frustrating journey because many healthcare providers may have limited experience with the identification and diagnosis of rare diseases. Also, diagnosis before the onset of symptoms or diagnosis in the early stages of the disease can be challenging. Living with a progressive and debilitating rare condition like Jansens’s can mean never fully sleeping at night. There is a constant anguish deep within. There are recurring surgeries to correct bending bones, endless battles with pain, and struggles with recovery and relapse. However, through it all, we focus on keeping life going, and find laughter and joy where we can. We surround ourselves in art and encourage the boys to pursue their creative talents as an outlet for their grief.

As the founder of The Jansen's Foundation, how have you been able to raise awareness about Jansen's and other rare skeletal diseases? What are some of the key initiatives you have undertaken?

I’ll need to provide some context for readers to understand the work we do and even then it will be skimming the surface of what we have managed to accomplish.

Over 30 million Americans have rare diseases, with over 93 per lacking FDA-approved therapies. Bringing a drug to the market can take 10 to 15 years and cost over US$2 billion, with less than 12 per cent gaining approval. For Jansen's, visibility seemed like a colossal challenge.

To raise awareness and advocate for our cause, I knew I had to share our story, my kids' journey, and seek funding. Although it seemed daunting and uncomfortable to open up about our personal struggles with strangers, it was essential to do so. In 2017, we took the first step by establishing The Jansen's Foundation and creating a social media presence to share our experiences.

I spoke at events, lobbied for research on Capitol Hill, and advocated for patients with rare disease. These efforts led to the first international conference on Jansen's disease and subsequently, multiple research publications. We secured a US$2 million RO1 grant for pre-clinical data and a mouse model. In 2018, we met the FDA for a pre-IND, and in 2019, we obtained funding for toxicology studies. Now, in 2023, we hope for the first human trial for Jansen's disease, a vital step towards a cure.

Of what we know, major pharmaceutical companies often focus on diseases that affect large populations. How has your experience been navigating the pharmaceutical industry and other challenges to garner support?

Although individually uncommon, collectively, rare diseases affect a huge number of people—roughly 350-400 million people worldwide, or between 5-10 per cent  of the world’s population. What’s more, these figures only include reported cases. The challenges of rare diseases are twofold. Firstly, their uneven distribution among populations makes it difficult to have a complete picture of their prevalence due to lopsided data in certain countries. Secondly, funding is a major hurdle as rare diseases are often considered lower priorities, resulting in underserved drug development and the designation of drugs as ‘orphan drugs’. While initiatives like the US’s  Orphan Drug Act has brought many new drugs to the market, they have led to a pricing crisis, making them prohibitively expensive for patients. Cost-effective solutions are needed to address the various challenges associated with researching and developing treatments for rare diseases in today's changing market.

Even with the FDA approving more orphan drugs, access and affordability can still be issues. What more do you think needs to be done?

Among the many barriers to access are a lack of transparency in pricing, inefficient regulatory processes, as well as barriers along the patient access pathway which include lack of reimbursement, diagnostic challenges, limited knowledge of treatment options, and the absence of infrastructure to manage administration and monitor use. Patients with rare diseases often have limited or no options for approved treatments or participation in clinical trials. In such cases, expanded access (or “compassionate use”) provides a potential means of accessing unapproved investigational medicines. It is also possible to capture and analyse clinical data from such use, but doing so is controversial. Harmonisation across the globe of expanded access regulations could reduce manufacturer burdens, improve patient access, and yield better data. These changes would better balance the need to generate quality evidence with the desire for pre-approval access to investigational medicine. This is what drives our foundation; they have become sort of our mandate.

For readers who might be overwhelmed by your journey, is there any good news to share?

Certainly! A time of progress and hope is upon us. Biopharmaceutical researchers have leveraged new technologies and the growing scientific understanding of many rare diseases to develop groundbreaking therapies over the last 10 years. In the last decade, more than 230 new orphan drugs were approved by the US Food and Drug Administration (FDA). In 2015 alone, nearly half (47 per cent) of novel drug approvals were for rare diseases. We are on an incredible journey to find our miracle cure that will not only help our boys but bring hope to many others with rare skeletal diseases. We believe in miracles.

You are clearly a mother on a mission—a superhero if you ask us. What message do you have for our readers who are reading about Jansen’s for the first time?

There’s a lot of work still to be done and we are just getting started. Living with a rare disease can be overwhelming, but it's essential to never lose faith. Together, we can overcome the challenges and create a better future for those affected by such conditions. Let's join hands, raise awareness, and advocate for the much-needed research and support. Every step we take brings us closer to finding a cure and improving the lives of countless individuals. 

Note: Physical irregularities often associated with Jansen's also include the following: Prominent or protruding eyes, a high-arched palate, micrognathia or smallness of the jaws [particularly the lower (mandible) jaw], impacted teeth and poor enamel. Thickening of the back of the skull can also cause pressure on the optic nerve and lead to loss of eyesight and hearing. Because calcium is lost faster than it can be absorbed by the bones, patients with Jansen’s also suffer from nephrocalcinosis (accumulation of calcium in the interstitium of the kidney).

Teams of orthopedic experts, geneticists, nephrologists, therapists, scientists and researchers work together to make life manageable. And while all known patients affected by this condition have their superhero moments, an honest insight into their lives is important to know why Nizar, and others, are chasing a cure—aggressively.

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