Frederick S. Kaplan is an American medical doctor specializing in research of muscoskeletal disorders such as fibrodysplasia ossificans progressiva (FOP).
Fibrodysplasia ossificans progressiva (FOP) is an extremely rare connective tissue disease. It is a severe, disabling disease with no cure or treatment and is the only known medical condition where one organ system changes into another.
Frederick Kaplan received a bachelor's degree from Johns Hopkins University in 1972. He also obtained his Doctor of Medicine (MD) from Johns Hopkins University, graduating in 1976.
A bachelor's degree or baccalaureate is an undergraduate academic degree awarded by colleges and universities upon completion of a course of study lasting three to seven years. In some institutions and educational systems, some bachelor's degrees can only be taken as graduate or postgraduate degrees after a first degree has been completed. In countries with qualifications frameworks, bachelor's degrees are normally one of the major levels in the framework, although some qualifications titled bachelor's degrees may be at other levels and some qualifications with non-bachelor's titles may be classified as bachelor's degrees.
The Johns Hopkins University is a private research university in Baltimore, Maryland. Founded in 1876, the university was named for its first benefactor, the American entrepreneur, abolitionist, and philanthropist Johns Hopkins. His $7 million bequest —of which half financed the establishment of Johns Hopkins Hospital—was the largest philanthropic gift in the history of the United States up to that time. Daniel Coit Gilman, who was inaugurated as the institution's first president on February 22, 1876, led the university to revolutionize higher education in the U.S. by integrating teaching and research. Adopting the concept of a graduate school from Germany's ancient Heidelberg University, Johns Hopkins University is considered the first research university in the United States. Over the course of several decades, the university has led all U.S. universities in annual research and development expenditures. In fiscal year 2016, Johns Hopkins spent nearly $2.5 billion on research.
A Doctor of Medicine is a medical degree, the meaning of which varies between different jurisdictions. In the United States, Canada and other countries, the MD denotes a professional graduate degree awarded upon graduation from medical school. In the United Kingdom, Ireland and other countries, the MD is a research doctorate, higher doctorate, honorary doctorate or applied clinical degree restricted to those who already hold a professional degree in medicine; in those countries, the equivalent professional degree is typically titled Bachelor of Medicine, Bachelor of Surgery (MBBS).
In the mid 1980s, Kaplan met David Romanoff, the medical director of the Inglis House—a residential care facility for adults with disabilities. Two residents of the facility were diagnosed with fibrodysplasia ossificans progressiva (FOP), a very rare medical condition in which the soft tissue of the body ossifies, or turns to bone, over time. Romanoff was "grappling" with caring for the patients, and asked Kaplan if he would like to meet them, which he did. This was his first encounter with the disease beyond reading about it.
In anatomy, soft tissue includes the tissues that connect, support, or surround other structures and organs of the body, not being hard tissue such as bone. Soft tissue includes tendons, ligaments, fascia, skin, fibrous tissues, fat, and synovial membranes, and muscles, nerves and blood vessels.
Ossification in bone remodeling is the process of laying down new bone material by cells called osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the formation of normal, healthy bone tissue: Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor. In fracture healing, endochondral osteogenesis is the most commonly occurring process, for example in fractures of long bones treated by plaster of Paris, whereas fractures treated by open reduction and internal fixation with metal plates, screws, pins, rods and nails may heal by intramembranous osteogenesis.
In 1988, Kaplan met immunologist and geneticist Michael Zasloff; Zasloff introduced him to a patient with FOP, a young child.Kaplan stated that his reaction to meeting the young patient was "visceral and immediate", causing him to request a three-year sabbatical from his work so that he could begin to research FOP. Together, Zasloff and Kaplan collaborated to create the FOP Collaborative Research Project at the University of Pennsylvania. In 1992, Kaplan and Eileen Shore initiated the FOP Research Laboratory.
Michael A. Zasloff is an American physician, medical researcher, and entrepreneur. Zasloff is primarily known for his work on antimicrobial peptides.
A Sabbatical is a rest or break from work.
Eileen Shore is an American medical researcher and geneticist specializing in research of muscoskeletal disorders such as fibrodysplasia ossificans progressiva.
In 2006, Shore and Kaplan discovered the cause of FOP, publishing their findings as "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva".The cause of the disease was traced to a single mutation in the activin A receptor, type I gene. After the discovery, Kaplan remarked, "It took our team of researchers and collaborators more than 15 years of diligent effort to unravel the genetic cause of FOP, which had been shrouded in mystery for so long."
Activin A receptor, type I (ACVR1) is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2. ACVR1 has been linked to the 2q23-24 region of the genome. This protein is important in the bone morphogenic protein (BMP) pathway which is responsible for the development and repair of the skeletal system. While knock-out models with this gene are in progress, the ACVR1 gene has been connected to Fibrodysplasia Ossificans Progressiva, a disease characterized by the formation of heterotopic bone throughout the body.
As of 2015, Kaplan and Shore were the directors of the Center for Research in FOP and Related Disorders. They are considered the "world’s foremost experts on FOP".
In 1994, Kaplan and his colleagues authored a publication describing a new muscoskeletal disorder, progressive osseous heteroplasia (POH).POH was discovered as a distinct condition when Kaplan was investigating FOP. Some of the patients initially diagnosed with FOP were found to have a distinctly different manifestation of symptoms, though, like FOP, the disease still resulted in heterotopic ossification (formation of bone tissue outside the skeleton). None of the patients had congenital abnormalities of the big toe, which is a diagnostic feature for FOP. All of the patients also had ossification of the skin during infancy, which did not occur in FOP. Also, the pattern of ossification was different in these patients, spreading in an intramembranous fashion rather than endochondral.
In 2006, the magazine Newsweek named Kaplan as one of their "15 People Who Make America Great".In 2009, he was elected to the National Academy of Medicine. In 2017, Kaplan received the Rare Impact Award from the National Organization for Rare Disorders. In 2018, he received the Grand Hamdan International Award via the Sheikh Hamdan bin Rashid Al Maktoum Award for Medical Sciences for his work in medical sciences.
Arachnoiditis is an inflammatory condition of the arachnoid mater or 'arachnoid', one of the membranes known as meninges that surround and protect the nerves of the central nervous system, including the brain and spinal cord. The arachnoid can become inflamed because of adverse reactions to chemicals, infection from bacteria or viruses, as the result of direct injury to the spine, chronic compression of spinal nerves, complications from spinal surgery or other invasive spinal procedures, or the accidental intrathecal injection of steroids intended for the epidural space. Inflammation can sometimes lead to the formation of scar tissue and adhesion that can make the spinal nerves "stick" together, a condition where such tissue develops in and between the leptomeninges. The condition is extremely painful, especially when progressing to adhesive arachnoiditis. Another form of the condition is arachnoiditis ossificans, in which the arachnoid becomes ossified, or turns to bone, and is thought to be a late-stage complication of the adhesive form of arachnoiditis.
The Perelman School of Medicine, commonly known as Penn Med, is the medical school of the University of Pennsylvania. It is located in the University City section of Philadelphia. Founded in 1765, the Perelman School of Medicine is the oldest medical school in the United States and is one of the seven Ivy League medical schools. Penn Med consistently ranks among the highest recipients of NIH research awards, and it currently ties for 6th place on U.S. News & World Report's "Best Medical Schools: Research" list.
Köhler disease is a rare bone disorder of the foot found in children between six and nine years of age. The disease typically affects boys, but it can also affect girls. It was first described in 1908 by Alban Köhler (1874–1947), a German radiologist. Dr. A. Köhler noted that children with foot pain displayed characteristics within their x-rays of irregularity in growth and development of the tarsal navicular bone in the foot. Furthermore, Köhler disease is known to affect five times more boys than girls and typically, only one foot is affected. The disease was then found to belong to a group of conditions called osteochondroses, which disturb bone growth at ossification centres which occurs during bone development.
Myositis ossificans comprises two syndromes characterized by heterotopic ossification (calcification) of muscle.
Heterotopic ossification (HO) is the process by which bone tissue forms outside of the skeleton.
Bone morphogenetic protein 5 is a protein that in humans is encoded by the BMP5 gene.
Keutel syndrome (KS) is a rare autosomal recessive genetic disorder characterized by abnormal diffuse cartilage calcification, hypoplasia of the mid-face, peripheral pulmonary stenosis, hearing loss, short distal phalanges (tips) of the fingers and mild mental retardation. Individuals with KS often present with peripheral pulmonary stenosis, brachytelephalangism, sloping forehead, midface hypoplasia, and receding chin. It is associated with abnormalities in the gene coding for matrix gla protein (MGP). Being an autosomal recessive disorder, it may be inherited from two unaffected, abnormal MGP-carrying parents. Thus, people who inherit two affected MGP genes will likely inherit KS.
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle. Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine function. Conversely, inhibin downregulates FSH synthesis and inhibits FSH secretion. The existence of inhibin was hypothesized as early as 1916; however, it was not demonstrated to exist until Neena Schwartz and Cornelia Channing's work in the mid 1970s, after which both proteins were molecularly characterized ten years later.
Harry Raymond Eastlack, Jr. was the subject of the most recognized case of FOP from the 1900s. His case is also particularly acknowledged, by scientists and researchers, for his contribution to medical advancement. After suffering from a rare, disabling, and currently incurable genetic disease, Eastlack decided to have his skeleton and medical history donated to the Mütter Museum of the College of Physicians of Philadelphia in support of FOP research. His skeleton is one of the few FOP-presenting, fully articulated ones in existence, and it has proved valuable to the study of the disease.
Progressive osseous heteroplasia is a cutaneous condition characterized by cutaneous or subcutaneous ossification.
The International Fibrodysplasia Ossificans Progressiva Association (IFOPA) is a US-based 501(c)(3) non-profit organization supporting medical research, education and communication for those afflicted by the rare genetic condition Fibrodysplasia Ossificans Progressiva (FOP). IFOPA's mission is to fund research to find a cure for FOP while supporting, connecting, and advocating for individuals with FOP and their families, and raising awareness worldwide. IFOPA is governed by a volunteer board of directors which may range in number from 9 to 15, at least one of whom must have FOP. The association's location is 1520 Clay St., Suite H2, North Kansas City, MO, 64116, part of the Kansas City, Missouri metropolitan area.
Opsismodysplasia is a type of skeletal dysplasia first described by Zonana and associates in 1977, and designated under its current name by Maroteaux (1984). Derived from the Greek opsismos ("late"), the name "opsismodysplasia" describes a delay in bone maturation. In addition to this delay, the disorder is characterized by micromelia, particularly of the hands and feet, delay of ossification, platyspondyly, irregular metaphyses, an array of facial aberrations and respiratory distress related to chronic infection. Opsismodysplasia is congenital, being apparent at birth. It has a variable mortality, with some affected individuals living to adulthood. The disorder is rare, with an incidence of less than 1 per 1,000,000 worldwide. It is inherited in an autosomal recessive pattern, which means the defective (mutated) gene that causes the disorder is located on an autosome, and the disorder occurs when two copies of this defective gene are inherited. No specific gene has been found to be associated with the disorder. It is similar to spondylometaphyseal dysplasia, Sedaghatian type.
Palovarotene is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for fibrodysplasia ossificans progressiva (FOP), an ultra-rare and severely disabling genetic disease characterized by extra-skeletal bone formation in muscle and soft tissues.
FOP Friends, formerly Friends of Oliver, is a registered charity in the United Kingdom established on 1 March 2012. It aims to raise funds that are needed to find effective treatments for the rare genetic condition Fibrodysplasia Ossificans Progressiva (FOP). The charity also works to raise awareness and understanding of FOP amongst medical communities and the general public.