Mild Ol - Toward Better Understanding and Treatment

描述（由申请人提供）： 成骨不全是一种临床和遗传异质性骨疾病。表型范围从围产期的致死性到极轻度的罕见骨折。大多数受影响的个体在两个I型胶原基因COL 1A 1和COL 1A 2中具有突变，但约10-15%在其他基因中具有突变，其中没有一个尚未被鉴定或表征。迄今为止，研究兴趣和临床关注都集中在早期死亡或严重残疾是规则的严重形式。治疗试验正在进行中，以确定可能改变结构异常胶原合成时导致的骨骼特征的药物治疗。这些疗法包括使用双膦酸盐来减缓骨转换和细胞置换，迄今为止，所有这些疗法的疗效都不确定。基因治疗方法，包括携带突变的等位基因的失活，提供了另一条研究路线，其基本思想是将严重形式的OI转化为由单倍性不足引起的较温和形式。这种方法假设“单倍不足”的自然史是众所周知的，治疗将是有效的，并且结果可以预测。令人惊讶的是，虽然在美国估计有20- 40，000人患有OI，但大多数人都患有轻度形式的疾病，但自然史并没有得到很好的理解，主要并发症的频率仍然不确定，有效治疗的前景仍然未被探索，并且这种疾病对家庭和美国医疗保健系统的财政影响仍然没有得到表征。为了研究这些和相关问题，由医学博士Peter Byers和医学博士Michael Whyte主持的为期一天的会议“轻度OI --走向更好的理解和治疗”将于2004年4月19日在芝加哥与ASCI和AAP会议同时举行。本次会议将汇集25名研究人员，研究如何进一步研究轻度OI的个人和家庭，以更好地了解这种疾病和相关疾病的异质性和潜在缺陷，并制定一种评估和治疗方法，反映目前对更严重形式的关注。

DESCRIPTION (provided by applicant): Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder of bone. The phenotypes range from lethal in the perinatal period to an extremely mild presentation with rare fractures. The majority of affected individuals have mutations in the two type I collagen genes, COL1A1 and COL1A2 but about 10-15% have mutations in other genes, none of which have yet been identified or characterized. To date, both research interest and clinical concern have centered around the severe forms in which early death or severe disability are the rule. Treatment trials are in process to identify medical therapies that may alter the character of bone that results when structurally abnormal collagens are synthesized. These therapies include the use of bisphosphonates to slow bone turnover, and cell replacement, all, to date, with uncertain therapeutic efficacy. Gene therapeutic approaches, including inactivation of the mutation bearing alleles provides another line of investigation with the underlying idea being to convert a severe form of OI to a milder form that results from haploinsufficiency. This approach assumes that the natural history of 'haploinsufficiency is well known, that therapies will be effective, and that outcomes can be predicted. Surprisingly, although the majority of the estimated 20-40,000 people in the US with OI have the mild forms of the condition, the natural history is not well appreciated, the frequency of major complications remains uncertain, the prospects for effective therapies remains unexplored, and the fiscal impact of the disorder on the family and the US health care system remain uncharacterized. To examine these and related issues, a one -day meeting "Mild OI - Toward Better Understanding and Treatment" chaired by Peter Byers, MD and Michael Whyte, MD will be held in Chicago on April 19, 2004, in conjunction with the ASCI and AAP meetings. This meeting will bring together 25 investigators to examine how further study of individuals and families with mild forms of OI will provide greater insight into the heterogeneity and underlying defects in this and related disorders and develop an approach to their assessment and treatment that mirrors the attention currently being paid to the more severe forms.